Derivatives of n-phenylpyrazoles

ABSTRACT

N-Phenylpyrazole derivatives of the formula:   &lt;IMAGE&gt; I  wherein R1 represents cyano, nitro, halogen, acetyl or formyl; R2 represents R5SO2, R5SO or R5S in which R5 is optionally halogen substituted alkyl, alkenyl or alkynyl; R3 represents a hydrogen atom or a group NR6R7 wherein R6 and R7 each represent hydrogen, alkyl, alkenylalkyl, alkynylalkyl, formyl, optionally halogen substituted alkanoyl, optionally halogen substituted alkoxycarbonyl, or alkoxymethyleneamino, halogen, or R6 and R7 together form a cyclic imide and R4 represents a substituted phenyl group possess arthropodicidal, plant nematocidal, anthelmintic and anti-protozoal properties; their preparation, compositions containing them and their use are described.

This application is a divisional of application Ser. No. 08/057,669,filed May 5, 1993, now allowed which is a divisional of application Ser.No. 07/520,290, filed May 7, 1990, now U.S. Pat. No. 5,232,940, which isa continuation-in-part of application Ser. No. 07/445,153, filed Dec. 5,1989, and now abandoned, which is in turn a continuation of Ser. No.06/943,132, filed Dec. 17, 1986, and now abandoned; Ser. No. 07/520,290further being a continuation of Ser. No. 07/380,333, filed Jul. 17,1989, and now abandoned, which is in turn a continuation of Ser. No.07/205,299, filed June 10, 1988, and now abandoned; and Ser. No.07/520,290 further being a continuation of Ser. No. 07/413,134, filedSep. 27, 1989, and now abandoned, which is in turn a continuation ofSer. No. 07/205,238, filed Jun. 10, 1988, and now abandoned.

BACKGROUND OF THE INVENTION

This invention relates to N-phenylpyrazole derivatives, to compositionscontaining them and to the use of N-phenylpyrazole derivatives againstarthropod, plant nematode, helminth and protozoan pests.

In J. Heter, Chem., 12 (1975) 1199-1205, P. L. Southwick and B. Dhawanhave described experiments for the preparation of4,6-diamino-pyrazolo[3,4-d]pyrimidines in the expectation that suchpyrimidine derivatives would have useful pharmacological properties.They employed as starting materials 5-amino-4-cyanopyrazoles carrying onthe 1-position a hydrogen atom, a methyl group, a hydroxyethyl group ora phenyl group substituted by one or more chlorine atoms and/or methylgroups, and on the 3-position a hydrogen atom, a methyl group or aphenyl or benzyl group. This publication contains no suggestion thatcompounds of general formula I possess or would be expected to possessactivity against arthropods, helminths or plant nematodes.

Apparently these pyrazole compounds did not lead (according to theauthors of the article) to useful therapeutic (viz. antimalarial)4,6-diaminopyrazolo[3,4-d]pyrimidines.

U.S. Pat. No. 3,760,084 describes certain 5-amino-1-phenyl-pyrazoles asbeing useful for ameliorating inflammation in warm-blooded animals: thecompounds carry on the 3-position hydrogen or a lower alkyl group and onthe 4-position a carbamoyl or cyano group.

U.S. Pat. No. 3,869,274 describes certain 4-nitropyrazoles as beinguseful for the induction of abscission of fruit from fruit-bearingplants.

U.S. Pat. No. 4,066,776 describes a very extensive group of1,4-disubstituted-3-nitropyrazoles as having antimicrobial,parasiticidal and herbicidal properties: the great biological activityof the compounds is stated to be limited to the 3-nitropyrazolesdisclosed, the characterizing feature of the compounds being the3-nitropyrazole nucleus.

Japanese Patent Publication No. 12644/64 describes a process for thepreparation of 4-thiocyanatopyrazole derivatives which are stated to beuseful as germicides.

Japanese Patent Publication No. 49-117502 describes certain pyrazolesulphonamides having anti-thrombogenic properties.

None of the foregoing publications describes or suggests that compoundsof general formula I possess or would be expected to possess theactivity against arthropods, helminths or plant nematodes which has beendiscovered by the inventors.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention provides N-phenylpyrazole derivatives of thegeneral formula I wherein R¹ represents a cyano or nitro group, ahalogen, i.e. fluorine, chlorine, bromine or iodine atom, an acetyl orformyl group, a straight- or branched-chain alkyl group containing from1 to 4 carbon atoms which may be unsubstituted or substituted by one ormore halogen atoms or a cycloalkyl group containing from 3 to 6 carbonatoms; R² represents a group R'SO₂, R'SO, or R'S in which R' representsa straight- or branched-chain alkyl, alkenyl or alkynyl (preferably1-(alkynyl)alkyl and more preferably alk-2-ynyl) group containing up to6 carbon atoms which may be unsubstituted or substituted by one or morehalogen atoms which may be the same or different or R² is a halogen,i.e., fluorine, chlorine, bromine or iodine atom, the cyano or nitrogroup, a cycloalkyl group containing from 3 to 5 carbon atoms, astraight- or branched-chain alkenyl group containing from 2 to 6 carbonatoms, the thiocyanato group, the sulphamoyl group which may beunsubstituted or substituted by one or two straight- or branched-chainalkyl groups which may be the same or different and contain from 1 to 6carbon atoms, the carbamoyl group which may be unsubstituted orsubstituted by one or two straight- or branched-chain alkyl groups whichmay be the same or different and contain from 1 to 6 carbon atoms, astraight- or branched-chain alkoxycarbonyl containing from 2 to 7 carbonatoms, a straight- or branched-chain alkanoyl group containing from 2 to7 carbon atoms, or a straight- or branched-chain alkyl group containingfrom 1 to 6 carbon atoms which may be unsubstituted or substituted byone or more halogen atoms; R³ represents a hydrogen atom, or an aminogroup --NR"R"' wherein R" and R"', which may be the same or different,each represent a hydrogen atom or a straight- or branched-chainalkenylalkyl or alkynylalkyl group containing up to 5 carbon atoms, astraight- or branched-chain alkyl group (containing from 1 to 6 carbonatoms, and which may be unsubstituted or substituted by straight- orbranched-chain alkoxycarbonyl of 2 to 5 carbon atoms), a formyl group, astraight- or branched-chain alkanoyl group (which contains from 2 to 7carbon atoms and which may be optionally substituted with one or morehalogen atoms) or R" and R"', together with the nitrogen atom to whichthey are attached, form a 5 to 6 membered cyclic imide and isunsubstituted or substituted with one or more halogen atoms, or R³represents a straight- or branched-chain alkoxycarbonyl group (whichcontains from 2 to 7 carbon atoms and is unsubstituted or substituted byone or more halogen atoms), or R³ represents a straight- orbranched-chain alkoxymethyleneamino group containing from 2 to 5 carbonatoms which may be unsubstituted or substituted on methylene by astraight- or branched-chain alkyl group containing from 1 to 4 carbonatoms, or R³ represents a halogen, i.e., fluorine, chlorine, bromine oriodine, atom, cycloalkyl group containing from 3 to 6 carbon atoms, orcycloalkylcarbonyl group (which contains from 4 to 7 carbon atoms) orstraight- or branched-chain alkoxy carbonyl group (which contains from 2to 7 carbon atoms and themselves are unsubstituted or substituted by oneor more halogen atoms), or R³ represents a straight- or branched-chainalkylsulphenylamino group containing from 1 to 4 carbon atoms, or R³represents a straight- or branched-chain alkyl group containing from 1to 4 carbon atoms, the carboxy group or a straight- or branched-chainalkylthio, alkylsulphinyl or alkylsulphonyl group containing from 1 to 6carbon atoms which may be unsubstituted or substituted by one or morehalogen atoms, or R³ represents a straight- or branched-chainedtrialkylsilylmethyl group containing from 1 to 6 carbon atoms in eachalkyl group which may be the same or different, a trialkylsilyl groupcontaining from 1 to 6 carbon atoms in each alkyl group which may be thesame or different, or the cyano or nitro group; R⁴, R⁵, R⁶, R⁷ and R⁸may be the same or different and represent a halogen, i.e., fluorine,chlorine, bromine or iodine, atom, a straight- or branched-chain alkylor alkoxy group containing from 1 to 4 carbon atoms which may beunsubstituted or substituted by one or more halogen atoms (e.g. atrifluoromethyl or trifluoromethoxy group), a straight- orbranched-chain alkylthio or alkylsulphinyl group containing from 1 to 4carbon atoms which is substituted by one or more halogen atoms (e.g. atrifluoromethylthio or trifluoromethylsulphinyl group), the nitro orcyano group or a straight- or branched-chain alkylsulphonyl groupcontaining from 1 to 4 carbon atoms which may be unsubstituted orsubstituted by one or more halogen atoms (e.g. thetrifluoromethylsulphonyl group).

Compounds of general formula I, processes for their preparation,compositions containing them and methods for their use constitutefeatures of the present invention.

It is to be understood that the halogen atoms on the phenyl group may bethe same or different. When groups are substituted by more than onehalogen atom it is to be understood that the halogen atoms may be thesame or different.

In a preferred embodiment, the present invention providesN-phenylpyrazole derivatives of the general formula I wherein R¹represents a cyano or nitro group, a halogen, i.e. fluorine, chlorine,bromine or iodine, atom, or an acetyl or formyl group; R² represents agroup R'SO₂, R'SO, or R'S in which R' represents a straight or branchedchain alkyl, alkenyl or alkynyl (preferably 1-(alkynyl)alkyl and morepreferably alk-2-ynyl) group containing up to 4 carbon atoms which maybe unsubstituted or substituted by one or more halogen atoms which maybe the same or different; R³ represents a hydrogen atom, or an aminogroup --NR"R"' wherein R" and R"', which may be the same or different,each represent a hydrogen atom or a straight or branched chain alkyl,alkenylalkyl or alkynylalkyl group containing up to 5 carbon atoms, aformyl group, a straight or branched chain alkanoyl group (whichcontains from 2 to 5 carbon atoms and which may be optionallysubstituted by one or more halogen atoms) or R" and R"' together with henitrogen atom to which they are attached form a 5 or 6 membered cyclicimide, or represents a straight or branched-chain alkoxycarbonyl group(which contains from 2 to 5 carbon atoms and is unsubstituted orsubstituted by one or more halogen atoms), or R³ represents a straightor branched-chain alkoxymethyleneamino group containing from 2 to 5carbon atoms which may be unsubstituted or substituted on methylene by astraight or branched-chain alkyl group containing from 1 to 4 carbonatoms, or represents a halogen, i.e. fluorine, chlorine, bromine oriodine, atom; and R⁴ is a fluorine, chlorine, bromine or iodine atom; R⁶is a straight or branched chain alkyl or alkoxy group containing from 1to 4 carbon atoms which may be unsubstituted or substituted by one ormore halogen atoms which may be the same or different (thetrifluoromethyl and trifluoromethoxy groups are preferred), or achlorine or bromine atom; and R⁸ is hydrogen or a fluorine, chlorine,bromine or iodine atom, with the exclusion of the compound wherein R¹represents cyano, R² represents methanesulphonyl, R³ represents amino,R⁴ and R⁸ are chloro and R⁶ is trifluoromethyl (i.e., the phenyl ring is2,6-dichloro-4-trifluoromethylphenyl), which have valuable activityagainst arthropod, plant nematode, helminth and protozoan pests, moreparticularly by ingestion of above preferred compound(s) by thearthropods.

Highly preferred compounds of the first embodiment of general formula Iare those wherein R² represents an alkylsulphonyl/sulphinyl/thio groupwhich is optionally halogen substituted containing from 1 to 4 carbonatoms, or an alkenyl- or alkynyl-sulphinyl/sulphinyl/thio group which isoptionally halogen substituted and contains up to 4 carbon atoms,preferably a trifluoromethylthio or trifluoro methylsulphinyl group, R³represents the hydrogen atom, an amino or methylamino group and R¹represents a halogen atom or preferably the cyano or nitro group.

Compounds of general formula I wherein the phenyl group contains thetrifluoromethyl or trifluoromethoxy group, and R² represents anoptionally halogenated alkylsulphonyl/sulphinyl/thio group containingfrom 1 to 4 carbon atoms are highly preferred. Trifluoromethylthio,trifluoromethylsulphinyl and trifluoromethanesulphonyl are especiallypreferred for R².

Highly preferred compounds of the first embodiment of general formula Iare those with phenyl substitution which is 2,4,6-trichloro,2,6-dichloro-4-difluoromethoxy, 2-chloro-4-trifluoromethyl,2-bromo-6-chloro-4-trifluoromethyl, 2,6-dibromo-4-trifluoromethyl or2-bromo-4-trifluoromethyl.

Compounds of general formula I with 2,6-dichloro-4-trifluoromethyl or2,6-dichloro-4-trifluoromethoxy substitution of the phenyl group areespecially preferred.

Compounds of the first embodiment of general formula I which are ofparticular interest are:

1.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.

2.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-trifluoromethylthiopyrazole.

3.5-Amino-3-cyano-1-(2,6-dichloro-4-difluoromethoxyphenyl)-4-trifluoromethylthiopyrazole.

4.5-Amino-1-(2-chloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole.

5.5-Amino-3-cyano-1-(2,4,6-trichlorophenyl)-4-trifluoromethylthiopyrazole.

6.5-Amino-3-cyano-1-(2,6-dibromo-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.

7.5-Amino-1-(2-bromo-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole.

8.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-difluoromethylthiopyrazole.

9.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-heptafluoropropylthiopyrazole.

10.5-Amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole.

11.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trichloromethylthiopyrazole.

12.5-Amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.

13.5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.

14.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-fluoro-4-trifluoromethylthiopyrazole.

15.5-Amino-4-chlorodifluoromethylthio-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

16.5-Chloro-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.

17.5-Amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole.

18.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxymethyleneamino-4-trifluoromethylthiopyrazole.

19.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxyethylideneamino-4-trifluoromethylthiopyrazole.

20.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxymethyleneamino-4-methanesulphonylpyrazole.

21.5-Acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.

22.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(propionyl)amino-4-trifluoromethylthiopyrazole.

23.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-propionamido-4-trifluoromethylthiopyrazole.

24.5-Acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole.

25.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthio-5-trimethylacetamidopyrazole.

26.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(methoxycarbonyl)amino-4-trifluoromethylthiopyrazole.

27.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-4-trifluoromethylthiopyrazole.

28.5-Chloroacetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.

29.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-4-methanesulphonylpyrazole.

30.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-5-trimethylacetamidopyrazole.

31.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dimethylamino-4-trifluoromethylthiopyrazole.

32.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-isopropylamino-4-trifluoromethylthiopyrazole.

33.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-propylamino-4-trifluoromethylthiopyrazole.

34.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dipropylamino-4-trifluoromethylthiopyrazole.

35.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(propargyl)amino-4-trifluoromethylthiopyrazole.

36.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methylamino-4-methanesulphonylpyrazole.

37.5-Bromo-3-cyano-1-(2,6-dichloro-4-trifluoroethylphenyl)-4-trifluoromethanesulphonylpyrazole.

38.5-Bromo-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.

39.5-Bromo-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole.

40.5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole.

41.3-Bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole.

42.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.

43.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethanesulphonylpyrazole.

44.3-Cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-trifluoromethylthiopyrazole.

45.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4methanesulphonylpyrazole.

46.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-iodo-4-trifluoromethylthiopyrazole.

47.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-iodo-4-trifluoromethanesulphonylpyrazole.

48.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-iodo-4-methanesulphonylpyrazole.

49.1-(2,6-Dichloro-4-trifluoromethylphenyl)-3-iodo-4-methanesulphonylpyrazole.

50.1-(2,6-Dichloro-4-trifluoromethylphenyl)-3-iodo-4-trifluoromethylthiopyrazole.

51.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethanesulphonylpyrazole.

52.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphinylpyrazole.

53.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-trifluoromethanesulphonylpyrazole.

54.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-trifluoromethylsulphinylpyrazole.

55.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4trifluoromethylsulphinylpyrazole.

56.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4(1-methylprop-2-ynylsulphinyl)pyrazole.

57.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylsulphinylpyrazole.

58.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-isopropylsulphinylpyrazole.

59.5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphinylpyrazole.

60.5-Amino-4-tert-butanesulphonyl-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

61.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-propylamino-4-trifluoromethylsulphonylpyrazole.

62.5-Acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethanesulphonylpyrazole.

63.1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-nitropyrazole.

64.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-nitropyrazole.

65.1-(2,6-Dichloro-4-trifluoromethylphenyl)-3-nitro-4-trifluoromethylsulphinylpyrazole.

66.5-Amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-3-cyano-4-methanesulphonylpyrazole.

67.5-Amino-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-3-cyano-4-methanesulphonylpyrazole.

68.3-Acetyl-5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole.

69.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthiopyrazole.

70.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthiopyrazole.

71.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-propylthiopyrazole.

72.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-isopropylthiopyrazole.

73.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(2-methylpropylthio)pyrazole.

74.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(1-methylpropylthio)pyrazole.

75.4-Allylthio-5-amino-3-cyano-1-(2,6-dichloro-4trifluoromethylphenyl)pyrazole.

76.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(prop-2-ynylthio)pyrazole.

77.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(1-methylprop-2-ynylthio)pyrazole.

78.5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthiopyrazole.

79.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-tert-butylthiopyrazole.

80.5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylsulphinylpyrazole.

81.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethanesulphonylpyrazole.

82.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methylamino-4-trifluoromethylthiopyrazole.

83.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(N-ethoxycarbonyl-N-methyl)amino-4-trifluoromethylthiopyrazole.

84.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-trifluoroacetamido-4-trifluoromethylthiopyrazole.

85.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(ethoxycarbonylamino)-4-trifluoromethylthiopyrazole.

86.3-Acetyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.

87.1-(2,6-Dichloro-4-trifluoromethylphenyl)-3-formyl-4-trifluoromethylthiopyrazole.

88.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-formyl-4-trifluoromethylthiopyrazole.

89.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-fluoro-4-trifluoromethanesulphonylpyrazole.

90.5-Amino-3-cyano-4-dichlorofluoromethylthio-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

91.5-Amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethanesulphonylpyrazole.

92.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-pentafluoroethylthiopyrazole.

93.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dimethylamino-4-trifluoromethylsulphinylpyrazole.

94.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-iodo-4-trifluoromethylsulphinylpyrazole.

95.5-Bromo-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphinylpyrazole.

96.5-Acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphinylpyrazole.

97.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenl)-5-bis(ethoxycarbonyl)amino-4-trifluoromethanesulphonylpyrazole.

98.3-Cyano-1-(2,6,dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonylamino-4-trifluoromethanesulphonylpyrazole.

99.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxymethyleneamino-4-trifluoromethanesulphonylpyrazole.

100.5-Amino-4-(2-chloro-1,1,2-trifluoroethylthio)-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

101.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dimethylamino-4-trifluoromethanesulphonylpyrazole.

The numbers 1 to 101 are assigned to the above compounds foridentification and reference hereinafter.

In a second embodiment, the invention provides 4-nitro-N-phenylpyrazolederivatives of the formula XXVI wherein R⁸ represents a fluorine,chlorine or bromine atom, R⁶ represents a chlorine or bromine atom, or astraight- or branched-chain alkyl or alkoxy group containing from 1 to 4carbon atoms which may be unsubstituted or substituted by one or morehalogen atoms (e.g. a trifluoromethyl or trifluoromethoxy group), R⁴ isas defined for R⁸ or represents the hydrogen atom, R¹ represents ahalogen, i.e. fluorine, chlorine, bromine or iodine, atom, or the cyanoor nitro group, R³ represents the hydrogen atom, or the amino group--NR"R"' wherein R" and R"', which may be the same or different, eachrepresents the hydrogen atom or a straight- or branched-chain alkylgroup containing from 1 to 6 carbon atoms, the formyl group, a straight-or branched-chain alkanoyl group containing from 2 to 7 carbon atoms (orR" and R"' together form a 5 or 6 membered cyclic imide with thenitrogen atom to which they are attached) which may be unsubstituted orsubstituted by one or more halogen atoms, or a straight- orbranched-chain alkoxycarbonyl group containing from 2 to 7 carbon atoms,which may be unsubstituted or substituted by one or more halogen atoms,or R³ represents a straight- or branched-chain alkoxymethyleneaminogroup containing from 2 to 5 carbon atoms which may be unsubstituted orsubstituted on methylene by a straight- or branched-chain alkyl groupcontaining from 1 to 4 carbon atoms, or represents a fluorine, chlorine,bromine or iodine atom, have valuable activity against arthropod, plantnematode, helminth and protozoan pests, more particularly by ingestionof the compound(s) of formula XXVI by the arthropods.

Highly preferred compounds of the second embodiment of formula XXVI arethose wherein R⁴, R⁶ and R⁸ together represent 2,4,6-trichloro,2,6-dichloro-4-trifluoromethyl or 2,6-dichloro-4-trifluoromethoxysubstitution of the phenyl group.

Highly preferred compounds of the second embodiment are those wherein R³represents the hydrogen atom or --NR"R"', preferably an amino oracetamido group, R⁴, R⁶ and R⁸ together represent2-6-dichloro-4-trifluoromethyl or 2,6-dichloro-4-trifluoromethoxysubstitution of the phenyl group, and R¹ is as hereinbefore defined.

The following compounds of formula XXVI are of particular interest asinsecticides:

102.5-Acetamido-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole.

103.5-Acetamido-3-chloro-1-(2,6-dichloro-4-trifluoroomethylphenyl)-4-nitropyrazole.

104.5-Acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole.

105.5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole.

106.5-Amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole.

107.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole.

108.5-Bromo-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole.

The numbers 102 to 108 are assigned to the above compounds foridentification and reference hereinafter.

In a third preferred embodiment, the N-phenylpyrazole derivatives of thegeneral formula I depicted hereinafter include compounds wherein R²represents a halogen, i.e. fluorine, chlorine, bromine or iodine, atom,the cyano or nitro group or a group R'SO₂, R'SO or R'S in which R'represents a straight- or branched-chain alkyl group containing from 1to 6 carbon atoms which may be unsubstituted or substituted by one ormore halogen atoms, a cycloalkyl group containing from 3 to 5 carbonatoms, a straight- or branched-chain alkenyl group containing from 2 to6 carbon atoms, the thiocyanato group, the sulphamoyl group which may beunsubstituted or substituted by one or two straight- or branched-chainalkyl groups which may be the same or different and contain from 1 to 6atoms, the carbamoyl group which may be unsubstituted or substituted byone or two straight- or branched-chain alkyl groups which may be thesame or different and contain from 1 to 6 carbon atoms, a straight- orbranched-chain alkoxycarbonyl group containing from 2 to 7 carbon atoms,a straight- or branched-chain alkanoyl group containing from 2 to 7carbon atoms, or a straight- or branched-chain alkyl group containingfrom 1 to 6 carbon atoms which may be unsubstituted or substituted byone or more halogen atoms, R³ represents the hydrogen atom, or the aminogroup --NR"R"' wherein R" and R"', which may be the same or different,each represents a hydrogen atom or a straight- or branched-chain alkylgroup (containing from 1 to 6 carbon atoms, and which may beunsubstituted or substituted by straight- or branched-chainalkoxycarbonyl of 2 to 5 carbon atoms), cycloalkyl group containing from3 to 6 carbon atoms, formyl group, straight- or branched-chain alkanoylgroup (which contain from 2 to 7 carbon atoms or together form a 5 or 6membered cyclic imide with the nitrogen atom to which they are attachedand themselves may be unsubstitued or substituted by one or more halogenatoms) or cycloalkylcarbonyl group (which contain from 4 to 7 carbonatoms) or straight- or branched-chain alkoxycarbonyl groups (whichcontain from 2 to 7 carbon atoms and themselves are unsubstituted orsubstituted by one or more halogen atoms), or R³ represents a straight-or branched-chain alkylsulphenylamino group containing from 1 to 4carbon atoms, a straight- or branched-chain alkoxymethyleneamino groupcontaining from 2 to 5 carbon atoms which may be unsubstituted orsubstituted on methylene by a straight- or branched-chain alkyl groupcontaining from 1 to 4 carbon atoms, or represents a halogen, i.e.fluorine, chlorine, bromine or iodine, atom, a straight- orbranched-chain alkyl group containing from 1 to 4 carbon atoms, thecarboxy group, or a straight- or branched-chain alkylthio,alkylsulphinyl or alkylsulphonyl group containing from 1 to 6 carbonatoms which may be unsubstituted or substituted by one or more halogenatoms, or represents a straight- or branched-chain trialkylsilylmethylgroup containing from 1 to 6 carbon atoms in each alkyl group which maybe the same or different, a trialkylsilyl group containing from 1 to 6carbon atoms in each alkyl group which may be the same or different orthe cyano or nitro group, R⁴ -R⁸ each represent a halogen, i.e.fluorine, chlorine, bromine or iodine atom, a straight- orbranched-chain alkyl or alkoxy group containing from 1 to 4 carbon atomswhich may be unsubstituted or substituted by one or more halogen atoms(e.g. a trifluoromethyl or trifluoromethoxy group), a straight- orbranched-chain alkylthio or alkylsulphinyl group containing from 1 to 4carbon atoms which is substituted by one or more halogen atoms (e.g. atrifluoromethylthio or trifluoromethylsulphinyl group), the nitro orcyano group or a straight- or branched-chain alkylsulphonyl groupcontaining from 1 to 4 carbon atoms which may be unsubstituted orsubstituted by one or more halogen atoms (e.g. thetrifluoromethylsulphonyl group), and R¹ represents a halogen, i.e.fluorine, chlorine, bromine or iodine, atom, a cyano or nitro group or astraight- or branched-chain alkyl group containing from 1 to 4 carbonatoms which may be unsubstituted or substituted by one or more halogenatoms, or a cycloalkyl group containing from 3 to 6 carbon atoms, and,when R³ represents a carboxy group, salts thereof withpesticidally-acceptable bases provided that R¹, R² and R³ do notsimultaneously represent three groups of the same genus selected fromthe genera (i) nitro, (ii) cyano, (iii) halogen and (iv) unsubstitutedalkyl, have valuable activity against arthropod, plant nematode andhelminth pests, more particularly by ingestion of the compound(s) ofgeneral formula I by the arthropods.

By the term "salts with pesticidally-acceptable bases" is meant saltsthe cations of which are known and accepted in the art for the formationof salts of pesticidally active acids for agricultural or horticulturaluse. When intended for application to vertebrates to combat infection orinfestation by arthropods or helminths, the salts with bases used willbe non-toxic. By the term "non-toxic" is meant salts with bases thecations of which are innocuous to the vertebrates at the dosesadministered and which do not vitiate the beneficial effects produced bythe anion.

Preferably, the salts are water-soluble. Suitable salts with basesinclude alkali metal (e.g. sodium and potassium), alkaline earth metal(e.g. calcium and magnesium), ammonium and amine (e.g. diethanolamine,triethanolamine, octylamine, morpholine and dioctylmethylamine) salts.It is to be understood that where reference is made in the presentspecification to the compounds of general formula I such reference isintended to include also the salts with pesticidally-acceptable bases ofcompounds of general formula I where appropriate.

Preferred compounds of general formula I are those with phenylsubstitution which is 2,4,6-trichloro, 2,3,5,6-tetrachloro,2-chloro-4-trifluoromethyl, 2,3,5,6-tetrafluoro-4-trifluoromethyl,2,6-dichloro-4-trifluoromethylthio,2-chloro-3,5,6-trifluoro-4-trifluoromethyl,2,6-dichloro-3,5-difluoro-4-trifluoromethyl, 2,6-dichloro-4nitro,2,6-dichloro-4-trifluoromethylsulphinyl, 2,6-dichloro-4-methanesulphonyland 2,6-dichloro-4-trifluoromethanesulphonyl.

Compounds of general formula I wherein R⁴ -R⁸ represent2,6-dichloro-4-trifluoromethyl or 2,6-dichloro-4-trifluoromethoxysubstitution of the phenyl group are especially preferred.

Preferred compounds are those where

(a) R² and R¹ each represent a cyano group and R³ represents thehydrogen atom, the amino group --NR"R"' or an alkylsulphenylamino group,an alkoxymethyleneamino group which may be unsubstituted or substitutedon methylene by an alkyl group, a halogen atom, an alkyl group, thecarboxy group, an alkylthio, alkylsulphinyl or alkylsulphonyl groupwhich is optionally halogen substituted, a trialkylsilylmethyl group, atrialkylsilyl group or the nitro group;

(b) R² represents an alkylsulphonyl group which is optionally halogensubstituted, a cycloalkylsulphonyl group or an alkenylsulphonyl group,R³ represents the hydrogen atom, the amino group --NR"R"' or analkylsulphenylamino group, an alkoxymethyleneamino group which isunsubstituted or substituted on methylene by an alkyl group, a halogenatom, an alkyl group, the carboxy group, an alkylthio, alkylsulphinyl oralkylsulphonyl group which is optionally halogen substituted, atrialkylsilylmethyl group, a trialkylsilyl group or the cyano or nitrogroup and R¹ represents a halogen atom or the cyano or nitro group;

(c) R¹ represents the nitro group, R² represents the cyano or nitrogroup, a carbamoyl group or an alkoxycarbonyl group and R³ representsthe hydrogen atom, a halogen atom, an alkyl group, the carboxy group, analkylthio, alkylsulphinyl or alkylsulphony group which is optionallyhalogen substituted, a trialkylsilylmethyl group, a trialkylsilyl groupor the nitro group;

(d) R¹ represents a halogen atom, R² represents the cyano or nitrogroup, a carbamoyl group or an alkoxycarbonyl group and R³ representsthe hydrogen atom, the amino group --NR"R"' or an alkylsulphenylaminogroup, an alkoxymethyleneamino group which is unsubstituted orsubstituted on methylene by an alkyl group, a halogen atom, an alkylgroup, the carboxy group, an alkylthio, alkylsulphinyl or alkylsulphonylgroup which is optionally halogen substituted, a trialkylsilylmethylgroup, a trialkylsilyl group or the nitro group; and

(e) R¹ represents an alkyl group which is unsubstituted or substitutedby one or more halogen atoms or a cycloalkyl group, R² represents ahalogen atom, the cyano or nitro group, a group R'SO₂, R'SO or R'S, thethiocyanato group, a sulphamoyl group, a carbamoyl group, analkoxycarbonyl group, an alkanoyl group or an alkyl group which isunsubstituted or substituted by one or more halogen atoms. R³ representsthe hydrogen atom, the amino group --NR"R"' or an alkylsulphenylaminogroup, an alkoxymethyleneamino group which is unsubstituted orsubstituted on methylene by an alkyl group, a halogen atom, an alkylgroup, the carboxy group, an alkylthio, alkylsulphinyl or alkylsuphonylgroup which is optionally halogen substituted, a trialkylsilylmethylgroup, a trialkylsilyl group or the cyano or nitro group.

It will be appreciated that the groups listed above are as hereinbeforedefined earlier in the specification.

Compounds of general formula I wherein R¹ represents a trifluoromethylor methyl group are also preferred in this third embodiment.

Compounds of the third embodiment of general formula I which are ofparticular interest against arthropods are:

109. 5-Amino-3,4-dicyano-1-(2,4,6-trichlorophenyl)pyrazole

110.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole

111. 5-Amino-3,4-dicyano-1-(2,3,5,6-tetrachlorophenyl)pyrazole

112.5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazole

113.5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

114.5-Amino-3-chloro-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole

115.5-Amino-3-bromo-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole

116.5-Amino-3-iodo-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole

117.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-5-ethanesulphenylaminopyrazole

118.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-5-methoxymethyleneaminopyrazole

119.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-5-propoxymethyleneaminopyrazole

120.5-Acetamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole

121.5-Dichloroacetamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole

122.5-Cyclopropylcarbonamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole

123.5-Pentanamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole

124.5-Propionamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole

125. 5-Amino-1-(2-chloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole

126.5-Amino-3,4-dicyano-1-(2,3,5,6-tetrafluoro-4-trifluoromethylphenyl)pyrazole

127.5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-pentafluoroethylpyrazole

128.5-Amino-3-chlorodifluoromethyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyanopyrazole

129.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-3-difluoromethylpyrazole

130.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-trifluoromethylpyrazole

131.5-Amino-4-carbamoyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

132.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methoxycarbonyl-3-trifluoromethylpyrazole

133.5-Acetamido-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

134.1-(2,6-Dichloro-4-trifluoromethylphenyl)-3,4-dicyano-5-(2,2-dimethylpropionamido)-pyrazole

135.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxymethyleneamino-3-trifluoromethylpyrazole

136.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dimethylamino-3-trifluoromethylpyrazole

137.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonylmethylamino-3-trifluoromethylpyrazole

138.4-Cyano-5-methylamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

139.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(2,2-dimethylpropionamido)-3-trifluoromethylpyrazole

140.5-Amino-4-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

141.5-Bromo-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

142.5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-fluoromethylpyrazole

143.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethylpyrazole

144.5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-3-trifluoromethylpyrazole

145.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-3-trifluoromethylpyrazole

146.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(cyclopropanecarbonyl)amino-3-trifluoromethylpyrazole

147.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-cyclopropanecarbonamido-3-trifluoromethylpyrazole

148.5-Amino-4-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

149.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonylamino-3-trifluoromethylpyrazole

150.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

151.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-iodo-3-trifluoromethylpyrazole

152.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methyl-3-trifluoromethylpyrazole

153.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(N,N-dimethylsulphamoyl)-3-trifluoromethylpyrazole

154.5-Amino-4-cyano-3-cyclopropyl-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole

155.5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-heptafluoropropylpyrazole

156.5-Amino-3,4-dicyano-1-(2,6-dichloro-4-trifluoromethylthiophenyl)pyrazole

157.5-Amino-1-(2-chloro-3,5,6-trifluoro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole

158.5-Amino-1-(2,6-dichloro-3,5-difluoro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole

159.5-Amino-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-3,4-dicyanopyrazole

160.5-Amino-4-cyano-3-ethyl-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole

161.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-methylpyrazole

162.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-ethoxycarbonylpyrazole

163.5-Amino-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-methanesulphonyl-3-methylpyrazole

164.5-Amino-1-(2-chloro-3,5,6-trifluoro-4-trifluoromethylphenyl)-4-cyano-3-trifluoromethylpyrazole

165.5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylthiophenyl)-3-trifluoromethylpyrazole

166.5-Amino-3-chlorofluoromethyl-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole

167.5-Amino-4-cyano-1-(2,6-dichloro-3,5-difluoro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

168.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(1-ethoxyethylideneamino)-3-methylpyrazole

169.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-5-succinimidopyrazole

170.5-Acetamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-trifluoromethylpyrazole

171.5-Acetamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-methanesulphonylpyrazole

172. 5-Amino-1-(2,6-dichloro-4-nitrophenyl)-3,4-dicyanopyrazole

173.1-(2,6-Dichloro-4-trifluoromethylphenyl)-3,4-dicyano-5-methylaminopyrazole

174.1-(2,6-Dichloro-4-trifluoromethylphenyl)-3,4-dicyano-5-ethylaminopyrazole

175.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(N-methyl-N-ethoxycarbonylamino)-3-trifluoromethylpyrazole

176.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(N-acetyl-N-trimethylacetylamino)-3-trifluoromethylpyrazole

177.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(N-propionyl-N-trimethylacetylamino)-3-trifluoromethylpyrazole

178.1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethyl-5-trimethylacetylaminopyrazole

179.1-(2,6-Dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonylamino-4-nitro-3-trifluoromethylpyrazole

180.3-Chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-5-trimethylacetylaminopyrazole

181.3-Chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-5-bis(ethoxycarbonyl)aminopyrazole

182.3-Chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-5-ethoxycarbonylaminopyrazole

183.4-Cyano-diacetylamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

184.5-(N-Acetyl-N-ethoxycarbonylamino)-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

185.1-(2,6-Dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-3,4-dicyanopyrazole

186.1-(2,6-Dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-4-methanesulphonyl-3-trifluoromethylpyrazole

187.1-(2,6-Dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonylamino-4-methanesulphonyl-3-trifluoromethylpyrazole

188.1-(2,6-Dichloro-4-trifluoromethylphenyl)-3,4-dicyano-5-ethoxycarbonylaminopyrazole

189.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-iodo-3-trifluoromethylpyrazole

190.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-iodo-3-methylpyrazole

191.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-nitropyrazole

192.5-Acetamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethylpyrazole

193.1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethylpyrazole

194.1-(2,6-Dichloro-4-trifluoromethylphenyl)-3-methyl-4-methanesulphonylpyrazole

195. 4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-fluoropyrazole

196.1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-trifluoromethylpyrazole

197.5-Chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-3-trifluoromethylpyrazole

198.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(N-ethylsulphamoyl)-3-trifluoromethylpyrazole

199.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(N-methylsulphamoyl)-3-trifluoromethylpyrazole

200. 1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-cyano-3-nitropyrazole

201.1-(2,6-Dichloro-4-trifluoromethylphenyl)-3,4-dicyano-5-nitropyrazole

202.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-3-fluoropyrazole

203.5-Amino-3-chloro-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-cyanopyrazole

204.5-Amino-3-chloro-4-cyano-1-(2,6-dichloro-3,5-difluoro-4-trifluoromethylphenyl)pyrazole

205.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethyl-5-trimethylsilylpyrazole

206.5-tert.-Butyldimethylsilyl-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

207.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methylthio-3-trifluoromethylpyrazole

208.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethyl-5-trifluoromethylthiopyrazole

209.5-Carboxy-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

210.1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethyl-5-trimethylsilylpyrazole

211.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethyl-5-trimethylsilylmethylpyrazole

212.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methoxycarbonylamino-3-trifluoromethylpyrazole

213.1-(2,6-Dichloro-4-trifluoromethylphenyl)-4,5-dicyano-3-trifluoromethylpyrazole

214.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole

215.4-Acetyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

216.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylsulphinyl-3-trifluoromethylpyrazole

217.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulphinyl-3-trifluoromethylpyrazole

218.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulphinyl-3-methylpyrazole

219.5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylsulphinylphenyl)-3-trifluoromethylpyrazole

220.4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methylsulphinyl-3-trifluoromethylpyrazole

221.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulphonyl-3-trifluoromethylpyrazole

222.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulphonyl-3-methylpyrazole

223.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-propanesulphonylpyrazole

224.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trichloromethanesulphonyl-3-methylpyrazole

225.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthio-3-methylpyrazole

226.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-methylthiopyrazole

227.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-n-propylthio-3-methylpyrazole

228.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthio-3-trifluoromethylpyrazole

229.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthio-3-trifluoromethylpyrazole

230.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-thiocyanato-3-trifluoromethylpyrazole

231.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-thiocyanatopyrazole

232.5-Amino-4-cyano-1-(2,6-dichloro-4-methanesulphonylphenyl)-3-trifluoromethylpyrazole

233.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-trichloromethylthiopyrazole

234.4-Cyano-1-(2,6-dichloro-4-trifluoromethanesulphonylphenyl)-5-nitro-3-trifluoromethylpyrazole

235.1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-difluoromethyl-3-trifluoromethylpyrazole

236.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methyl-3-trifluoromethylpyrazole.

The numbers 109 and 236 are assigned to the above compounds foridentification and reference hereinafter.

Especially preferred compounds of the third embodiment of generalformula I are numbered: 110, 130, 145, 161, 179, 214 and 226.

According to a feature of the present invention, there is provided amethod for the control of arthropod, plant nematode, helminth orprotozoan pests at a locus which comprises the treatment of the locus(e.g. by application or administration) with an effective amount of acompound of general formula I, wherein the various symbols are ashereinbefore defined. The compounds of general formula I may, inparticular, be used in the field of veterinary medicine and livestockhusbandry and in the maintenance of public health against arthropods,helminths or protozoa which are parasitic internally or externally uponvertebrates, particularly warm-blooded vertebrates, for example man anddomestic animals, e.g. cattle, sheep, goats, equines, swine, poultry,dogs, cats and fishes, for example Acarina, including ticks (e.g. Ixodesspp., Boophilus spp. e.g. Boophilus microplus, Amblyomma spp., Hyalommaspp., Rhipicephalus spp. e.g. Rhipicephalus appendiculatus,Haemaphysalis spp., Dermacentor spp., Ornithodorus spp. (e.g.Ornithodorus moubata and mites (e.g. Damalinia spp., Dermahyssusgallinae, Sarcoptes spp. e.g. Sarcoptes scabiei, Psoroptes spp.,Chorioptes spp., Demodex spp., Eutrombicula spp.,); Diptera (e.g. Aedesspp., Anopheles spp., Musca spp., Hypoderma spp., Gasterophilus spp.,Simulium spp.); Hemiptera (e.g. Triatoma spp.); Phthiraptera (e.g.Damalinia spp., Linognathus spp.); Siphonaptera (e.g. Ctenocephalidesspp.); Dictyoptera (e.g. Periplaneta spp., Blatella spp.); Hymenoptera(e.g. Monomorium pharaonis); for example against infections of thegastro-intestinal tract caused by parasitic nematode worms, for examplemembers of the family Trichostrongylidae, Nippostrongylus brasiliensis,Trichinella spiralis, Haemonchus contortus, Trichostrongyluscolubriformis, Nematodirus battus, Ostertagia circumcincta,Trichostrongylus axei, Cooperia spp. and Hymenolepis nana; in thecontrol and treatment of protozoal diseases caused by, for example,Eimeria spp. e.g. Eimeria tenella, Eimeria acervulina, Eimeria brunetti,Eimeria maxima and Eimeria necatrix, Trypanosoma cruzi, Leishmania spp.,Plasmodium spp., Babesia spp., Trichomonadidae spp., Histomonas spp.,Giardia spp., Toxoplasma spp., Entamoeba histolytica and Theileria spp.;in the protection of stored products, for example cereals, includinggrain and flour, groundnuts, animal feedstuffs, timber and householdgoods, e.g. carpets and textiles, against attack by arthropods, moreespecially beetles, including weevils, moths and mites, for exampleEphestia spp. (flour moths), Anthrenus spp. (carpet beetles), Triboliumspp. (flour beetles), Sitophilus spp. (grain weevils) and Acarus spp.(mites), in the control of cockroaches, ants and termites and similararthropod pests in infested domestic and industrial premises and in thecontrol of mosquito larvae in waterways, wells, reservoirs or otherrunning or standing water; for the treatment of foundations, structureand soil in the prevention of the attack on buildings by termites, forexample, Reticulitermes spp., Heterotermes spp., Coptotermes spp.; inagriculture, against adults, larvae and eggs of Lepidoptera (butterfliesand moths), e.g. Heliothis spp. such as Heliothis virescens (tobaccobudworm), Heliothis armigera and Heliothis zea, Spodoptera spp. such asS.exempta, S.littoralis (Egyptian cotton worm), S. eridania (southernarmy worm), Mamestra configurata (bertha army worm); Earias spp. e.g.E.insulana (Egyptian bollworm), Pectinophora spp. e.g. Pectinophoragossypiella (pink bollworm), Ostrinia spp. such as O.nubilalis (Europeancornborer), Trichoplusia ni (cabbage looper), Pieris spp. (cabbageworms), Laphygma spp. (army worms), Agrotis and Amathes spp. (cutworms),Wiseana spp. (porina moth), Chilo spp. (rice stem borer), Tryporyza spp.and Diatraea spp. (sugar cane borers and rice borers), Sparganothispilleriana (grape berry moth), Cydia pomonella (codling moth), Archipsspp. (fruit tree tortrix moths), Plutella xylostella (diamond backmoth); against adult and larvae of Coleoptera (beetles) e.g.Hypothenemus hampei (coffee berry borer), Hylesinus spp. (bark beetles),Anthonomus grandis (cotton boll weevil), Acalymma spp. (cucumberbeetles), Lema spp., Psylliodes spp., Leptinotarsa decemlineata(Colorado potato beetle), Diabrotica spp. (corn rootworms), Gonocephalumspp. (false wire worms), Agriotes spp. (wireworms), Dermolepida andHeteronychus spp. (white grubs), Phaedon cochleariae (mustard beetle),Lissorhoptrus oryzophilus (rice water weevil), Meligethes spp. (pollenbeetles), Ceutorhynchus spp., Rhynchophorus and Cosmopolites spp. (rootweevils); against Hemiptera e.g. Psylla spp., Bemisia spp., Trialeurodesspp., Aphis spp., Myzus spp., Megoura viciae, Phylloxera spp., Adelgesspp., Phorodon humuli (hop damson aphid), Aeneolamia spp., Nephotettixspp. (rice leaf hoppers), Empoasca spp., Nilaparvata spp., Perkinsiellaspp., Pyrilla spp., Aonidiella spp. (red scales), Coccus spp.,Pseucoccus spp., Helopeltis spp. (mosquito bugs), Lygus spp., Dysdercusspp., Oxycarenus spp., Nezara spp.; Hymenoptera e.g. Athalia spp. andCephus spp. (saw flies), Atta spp. (leaf cutting ants); Diptera e.g.Hylemyia spp. (root flies), Atherigona spp. and Chlorops spp. (shootflies), Phytomyza spp. (leaf miners), Ceratitis spp. (fruit flies);Thysanoptera such as Thrips tabaci; Orthoptera such as Locusta andSchistocerca spp. (locusts) and crickets e.g. Gryllus spp. and Achetaspp.; Collembola e.g. Sminthurus spp. and Onychiurus spp. (springtails),Isoptera e.g. Odontotermes spp. (termites), Dermaptera e.g. Forficulaspp. (earwigs) and also other arthropods of agricultural significancesuch as Acari (mites) e.g. Tetranychus spp., Panonychus spp. and Bryobiaspp. (spider mites), Eriophyes spp. (gall mites), Polyphacotarsonemusspp.; Blaniulus spp. (millipedes), Scutigerella spp. (symphilids),Oniscus spp. (woodlice) and Triops spp. (crustacea); nematodes whichattack plants and trees of importance to agriculture, forestry andhorticulture either directly or by spreading bacterial, viral,mycoplasma or fungal diseases of the plants, root-knot nematodes such asMeloidogyne spp. (e.g. M. incognita); cyst nematodes such as Globoderaspp. (e.g. G. rostochiensis); Heterodera spp. (e.g. H. avenae);Radopholus spp. (e.g. R. similis); lesion nematodes such as Pratylenchusspp. (e.g. P. pratensis); Belonolaimus spp. (e.g. B. gracilis);Tylenchulus spp. (e.g. T. semipenetrans); Rotylenchulus spp, (e.g. R.reniformis); Rotylenchus spp. (e.g. R. robustus); Helicotylenchus spp.(e.g. H. multicinctus); Hemicycliophora spp. (e.g. H. gracilis);Criconemoides spp. (e.g. C. similis); Trichodorus spp. (e.g. T.primitivus); dagger nematodes such as Xiphinema spp. (e.g. X.diversicaudatum), Longidorus spp. (e.g. L. elongatus); Hoplolaimus spp.(e.g. H. coronatus); Aphelenchoides spp. (e.g. A. ritzema-bosi, A.besseyi); stem and bulb eelworms such as Ditylenchus spp. (e.g. D.dipsaci).

The invention also provides a method for the control of arthropod ornematode pests of plants which comprises the application to the plantsor to the medium in which they grow of an effective amount of a compoundof general formula I or a pesticidally acceptable salt thereof.

For the control of arthropods and nematodes, the active compound isgenerally applied to the locus in which arthropod or nematodeinfestation is to be controlled at a rate of about 0.1 kg to about 25 kgof active compound per hectare of locus treated. Under ideal conditions,depending on the pest to be controlled, the lower rate may offeradequate protection. On the other hand, adverse weather conditions,resistance of the pest and other factors may require that the activeingredient be used in higher proportions. In foliar application, a rateof 1 g to 1000 g/ha may be used.

When the pest is soil-borne, the formulation containing the activecompound is distributed evenly over the area to be treated in anyconvenient manner. Application may be made, if desired, to the field orcrop-growing area generally or in close proximity to the seed or plantto be protected from attack. The active component can be washed into thesoil by spraying with water over the area or can be left to the naturalaction of rainfall. During or after application, the formulation can, ifdesired, be distributed mechanically in the soil, for example byploughing or disking. Application can be prior to planting, at planting,after planting but before sprouting has taken place or after sprouting.

The compounds of general formula I may be applied in solid or liquidcompositions to the soil principally to contol those nematodes dwellingtherein but also to the foliage principally to control those nematodesattacking the aerial parts of the plants (e.g. Aphelenchoides spp. andDitylenchus spp. listed above).

The compounds of general formula I are of value in controlling pestswhich feed on parts of the plant remote from the point of application,e.g. leaf feeding insects are killed by the subject compounds applied toroots.

In addition the compounds may reduce attacks on the plant by means ofantifeeding or repellent effects.

The compounds of general formula I are of particular value in theprotection of field, forage, plantation, glasshouse, orchard andvineyard crops, of ornamentals and of plantation and forest trees, forexample, cereals (such as maize, wheat, rice, sorghum), cotton, tobacco,vegetables and salads (such as beans, cole crops, curcurbits, lettuce,onions, tomatoes and peppers), field crops (such as potato, sugar beet,ground nuts, soyabean, oil seed rape), sugar cane, grassland and forage(such as maize, sorghum, lucerne), plantations (such as of tea, coffee,cocoa, banana, oil palm, coconut, rubber, spices), orchards and groves(such as of stone and pip fruit, citrus, kiwifruit, avocado, mango,olives and walnuts), vineyards, ornamental plants, flowers and shrubsunder glass and in gardens and parks, forest trees (both deciduous andevergreen) in forests, plantations and nurseries.

They are also valuable in the protection of timber (standing, felled,converted, stored or structural) from attack by sawflies (e.g. Urocerus)or beetles (e.g. scolytids, platypodids, lyctids, bostrychids,cerambycids, anobiids), or termites, for example, Reticulitermes spp.,Heterotermes spp., Coptotermes spp.

They have applications in the protection of stored products such asgrains, fruits, nuts, spices and tobacco, whether whole, milled orcompounded into products, from moth, beetle and mite attack. Alsoprotected are stored animal products such as skins, hair, wool andfeathers in natural or converted form (e.g. as carpets or textiles) frommoth and beetle attack; also stored meat and fish from beetle, mite andfly attack.

The compounds of general formula I are of particular value in thecontrol of arthropods, helminths or protozoa which are injurious to, orspread or act as vectors of diseases in man and domestic animals, forexample those hereinbefore mentioned, and more especially in the controlof ticks, mites, lice, fleas, midges and biting, nuisance and myiasisflies. The compounds of general formula I are particularly useful incontrolling arthropods, helminths or protozoa which are present insidedomestic host animals or which feed in or on the skin or suck the bloodof the animal, for which purpose they may be administered orally,parenterally, percutaneously or topically.

Coccidiosis, a disease caused by infections by protozoan parasites ofthe genus Eimeria, is an important potential cause of economic loss indomestic animals and birds, particularly those raised or kept underintensive conditions. For example, cattle, sheep, pigs and rabbits maybe affected, but the disease is especially important in poultry, inparticular chickens.

The poultry disease is generally spread by the birds picking up theinfectious organism in droppings on contaminated litter or ground or byway of food or drinking water. The disease is manifested by hemorrhage,accumulation of blood in the ceca, passage of blood to the droppings,weakness and digestive disturbances. The disease often terminates in thedeath of the animal but the fowl which survive severe infections havehad their market value substantially reduced as a result of theinfection.

Administration of a small amount of a compound of general formula Ipreferably by combination with poultry feed is effective in preventingor greatly reducing the incidence of coccidiosis. The compounds areeffective against both the cecal form (caused by E. tenella) and theintestinal forms (principally caused by E. acervulina, E. brunetti, E.maxima and E. necatrix).

The compounds of general formula I also exert an inhibitory effect onthe oocysts by greatly reducing the number and or the sporulation ofthose produced.

The compositions hereinafter described for topical application to manand animals and in the protection of stored products, household goods,property and areas of the general environment may, in general,alternatively be employed for application to growing crops and cropgrowing loci and as a seed dressing.

Suitable means of applying the compounds of general formula I include:

to persons or animals infested by or exposed to infestation byarthropods, helminths or protozoa, by parenteral, oral or topicalapplication of compositions in which the active ingredient exhibits animmediate and/or prolonged action over a period of time against thearthropods, helminths or protozoa, for example by incorporation in feedor suitable orally-ingestible pharmaceutical formulations, edible baits,salt licks, dietary supplements, pour-on formulations, sprays, baths,dips, showers, jets, dusts, greases, shampoos, creams, wax-smears andlivestock self-treatment systems; to the environment in general or tospecific locations where pests may lurk, including stored products,timber, household goods, and domestic and industrial premises, assprays, fogs, dusts, smokes, wax-smears, lacquers, granules and baits,and in tricklefeeds to waterways, wells, reservoirs and other running orstanding water; to domestic animals in feed to control fly larvaefeeding in their faeces;

to growing crops as foliar sprays, dusts, granules, fogs and foams; alsoas suspensions of finely divided and encapsulated compounds of generalformula I;

as soil and root treatments by liquid drenches, dusts, granules, smokesand foams; and

as seed dressings by liquid slurries and dusts.

The compounds of general formula I may be applied to control arthropods,helminths or protozoa in compositions of any type known to the artsuitable for internal or external administration to vertebrates orapplication for the control of arthropods in any premises or indoor oroutdoor area, containing as active ingredient at least one compound ofgeneral formula I in association with one or more compatible diluents oradjuvants appropriate for the intended use. All such compositions may beprepared in any manner known to the art.

Compositions suitable for administration to vertebrates or man includepreparations suitable for oral, parenteral, percutaneous, e.g. pour-on,or topical administration.

Compositions for oral administration comprise one or more of thecompounds of general formula I in association with pharmaceuticallyacceptable carriers or coatings and include, for example, tablets,pills, capsules, pastes, gels, drenches, medicated feeds, medicateddrinking water, medicated dietary supplements, slow-release boluses orother slow-release devices intended to be retained within thegastro-intestinal tract. Any of these may incorporate active ingredientcontained within microcapsules or coated with acid-labile oralkali-labile or other pharmaceutically acceptable enteric coatings.Feed premixes and concentrates containing compounds of the presentinvention for use in preparation of medicated diets, drinking water orother materials for consumption by animals may also be used.

Compositions for parenteral administration include solutions, emulsionsor suspensions in any suitable pharmaceutically acceptable vehicle andsolid or semisolid subcutaneous implants or pellets designed to releaseactive ingredient over a protracted period and may be prepared and madesterile in any appropriate manner known to the art.

Compositions for percutaneous and topical administration include sprays,dusts, baths, dips, showers, jets, greases, shampoos, creams,wax-smears, or pour-on preparations and devices (e.g. ear tags) attachedexternally to animals in such a way as to provide local or systemicarthropod control.

Solid or liquid baits suitable for controlling arthropods comprise oneor more compounds of general formula I and a carrier or diluent whichmay include a food substance or some other substance to inducecomsumption by the arthropod.

Liquid compositions include water miscible concentrates, emulsifiableconcentrates, flowable suspensions, wettable or soluble powderscontaining one or more compounds of general formula I which may be usedto treat substrates or sites infested or liable to infestation byarthropods including premises, outdoor or indoor storage or processingareas, containers or equipment and standing or running water.

Solid homogenous or heterogenous compositions containing one or morecompounds of general formula I, for example granules, pellets,briquettes or capsules, may be used to treat standing or running waterover a period of time. A similar effect may be achieved using trickle orintermittent feeds of water dispersible concentrates as describedherein.

Compositions in the form of aerosols and aqueous or non-aqueoussolutions or dispersions suitable for spraying, fogging and low- orultra-low volume spraying may also be used.

Suitable solid diluents which may be used in the preparation ofcompositions suitable for applying the compounds of general formula Iinclude aluminium silicate, kieselguhr, corn husks, tricalciumphosphate, powdered cork, absorbent carbon black, magnesium silicate, aclay such as kaolin, bentonite or attapulgite, and water solublepolymers and such solid compositions may, if desired, contain one ormore compatible wetting, dispersing, emulsifying or colouring agentswhich, when solid, may also serve as diluent.

Such solid compositions, which may take the form of dusts, granules orwettable powders, are generally prepared by impregnating the soliddiluents with solutions of the compound of general formula I in volatilesolvents, evaporating the solvents and, if necessary, grinding theproducts so as to obtain powders and, if desired, granulating orcompacting the products so as to obtain granules, pellets or briquettesor by encapsulating finely divided active ingredient in natural orsynthetic polymers, e.g. gelatin, synthetic resins and polyamides.

The wetting, dispersing and emulsifying agents which may be present,particularly in wettable powders, may be of the ionic or non-ionictypes, for example sulphoricinoleates, quaternary ammonium derivativesor products based upon condensates of ethylene oxide with nonyl- andoctylphenol, or carboxylic acid esters of anhydrosorbitols which havebeen rendered soluble by etherification of the free hydroxy groups bycondensation with ethylene oxide, or mixtures of these types of agents.Wettable powders may be treated with water immediately before use togive suspensions ready for application.

Liquid compositions for the application of the compounds of generalformula I may take the form of solutions, suspensions and emulsions ofthe compounds of general formula I optionally encapsulated in natural orsynthetic polymers, and may, if desired, incorporate wetting, dispersingor emulsifying agents. These emulsions, suspensions and solutions may beprepared using aqueous, organic or aqueous-organic diluents, for exampleacetophenone, isophorone, toluene, xylene, mineral, animal or vegetableoils, and water soluble polymers (and mixtures of these diluents), whichmay contain wetting, dispersing or emulsifying agents of the ionic ornon-ionic types or mixtures thereof, for example those of the typesdescribed above. When desired, the emulsions containing the compounds ofgeneral formula I may be used in the form of self-emulsifyingconcentrates containing the active substance dissolved in theemulsifying agents or in solvents containing emulsifying agentscompatible with the active substance, the simple addition of water tosuch concentrates producing compositions ready for use.

Compositions containing compounds of general formula I which may beapplied to control arthropod, plant nematode, helminth or protozoanpests, may also contain synergists (e.g. piperonyl butoxide or sesamex),stabilizing substances, other insecticides, acaricides, plantnematocides, anthelmintics or anticoccidials, fungicides (agriculturalor veterinary as appropriate e.g. benomyl, iprodione), bactericides,arthropod or vertebrate attractants or repellents or pheromones,reodorants, flavouring agents, dyes and auxiliary therapeutic agents,e.g. trace elements. These may be designed to improve potency,persistence, safety, uptake where desired, spectrum of pests controlledor to enable the composition to perform other useful functions in thesame animal or area treated.

Examples of other pesticidally-active compounds which may be includedin, or used in conjunction with, the compositions of the presentinvention are: acephate, chlorpyrifos, demeton-S-methyl, disulfoton,ethoprofos, fenitrothion, malathion, monocrotophos, parathion,phosalone, pirimiphos-methyl, triazophos, cyfluthrin, cypermethrin,deltamethrin, fenpropathrin, fenvalerate, permethrin, aldicarb,carbosulfan, methomyl, oxamyl, pirimicarb, bendiocarb, teflubenzuron,dicofol, endosulfan, lindane, benzoximate, cartap, cyhexatin,tetradifon, avermectins, ivermectin, milbemycins, thiophanate,trichlorfon, dichlorvos, diaveridine and dimetridazole.

The compositions for application to control arthropod, plant nematode,helminth or protozoan pests usually contain from 0.00001% to 95%, moreparticularly from 0.0005% to 50%, by weight of one or more compounds ofgeneral formula I or of total active ingredients (that is to say thecompound(s) of general formula I together with other substances toxic toarthropods and plant nematodes, anthelmintics, anticoccidials,synergists, trace elements or stabilisers). The actual compositionsemployed and their rate of application will be selected to achieve thedesired effect(s) by the farmer, livestock producer, medical orveterinary practitioner, pest control operator or other person skilledin the art. Solid and liquid compositions for application topically toanimals, timber, stored products or household goods usually contain from0.00005% to 90%, more particularly from 0.001% to 10%, by weight of oneor more compounds of general formula I. For administration to animalsorally or parenterally, including percutaneously solid and liquidcompositions normally contain from 0.1% to 90% by weight of one or morecompound of general formula I. Medicated feedstuffs normally containfrom 0.001% to 3% by weight of one or more compounds of general formulaI. Concentrates and supplements for mixing with feedstuffs normallycontain from 5% to 90%, and preferably from 5% to 50%, by weight of oneor more compounds of general formula I. Mineral salt licks normallycontain from 0.1% to 10% by weight of one or more compounds of generalformula I.

Dusts and liquid compositions for application to livestock, persons,goods, premises or outdoor areas may contain 0.0001% to 15%, and moreespecially 0.005% to 2.0%, by weight of one or more compounds of generalformula I. Suitable concentrations in treated waters are between 0.0001ppm and 20 ppm, and more especially 0.001 ppm to 5.0 ppm. of one or morecompounds of general formula I and may also be used therapeutically infish farming with appropriate exposure times. Edible baits may containfrom 0.01% to 5% and preferably 0.01% to 1.0%, by weight of one or morecompounds of general formula I.

When administered to vertebrates parenterally, orally or by percutaneousor other means, the dosage of compounds of general formula I will dependupon the species, age and health of the vertebrate and upon the natureand degree of its actual or potential infestation by arthropod, helminthor protozoan pest. A single dose of 0.1 to 100 mg, preferably 2.0 to20.0 mg, per kg body weight of the animal or doses of 0.01 to 20.0 mg,preferably 0.1 to 5.0 mg, per kg body weight of the animal per day forsustained medication are generally suitable by oral or parenteraladministration. By use of sustained release formulations or devices, thedaily doses required over a period of months may be combined andadministered to animals on a single occasion.

In experiments on activity against arthropods carried out onrepresentative compounds of the first preferred embodiment, thefollowing results (wherein ppm indicates the concentration of thecompound in parts per million of the test solution applied) have beenobtained:

Test 1

One or more dilutions of the compounds to be tested were made in 50%aqueous acetone.

(a) Test species: Plutella xylostella (Diamond-back Moth) and Phaedoncochleariae (Mustard Beetle)

Turnip leaf discs were set in agar in petri-dishes and infected with 10larvae (2nd instar Plutella or 3rd instar Phaedon). Four replicatedishes were assigned to each treatment and were sprayed under a PotterTower with the appropriate test dilution. Four or five days aftertreatment the dishes were removed from the constant temperature (25° C.)room in which they had been held and the mean percentage mortalities oflarvae were determined. These data were corrected against themortalities in dishes treated with 50% aqueous acetone alone whichserved as controls.

(b) Megoura viciae (Vetch Aphid)

Potted tic bean plants previously infected with mixed stages of Megourawere sprayed to run-off using a laboratory turntable sprayer. Treatedplants were held in a greenhouse for 2 days and were assessed for aphidmortality using a scoring system, judging the response in comparisonwith plants treated with 50% aqueous acetone alone, as controls. Eachtreatment was replicated 4 times.

    ______________________________________                                        Score     3           all aphids dead                                                   2           few aphids alive                                                  1           most aphids alive                                                 0           no significant mortality                                ______________________________________                                    

(c) Test species: Spodoptera littoralis

French bean leaf discs were set in agar in petri-dishes and infectedwith 5 larvae (2nd instar). Four replicate dishes were assigned to eachtreatment and were sprayed under a Potter Tower with the appropriatetest dilution. After 2 days live larvae were transferred to similardishes containing untreated leaves set in agar. Two or three days laterthe dishes were removed from the constant temperature (25° C.) room inwhich they had been held and the mean percentage mortalities of larvaewere determined. These data were corrected against the mortalities indishes treated with 50% aqueous acetone alone which served as controls.

According to the above method an application of the following compoundswas effective against the larvae of Plutella xylostella producing atleast 65% mortality at less than 500 ppm: 1-10, 12-23, 25-27, 31-57,59-70, 76-79, 81-88, 90-92, 96, 101.

According to the above method an application of the following compoundswas effective against all stages of Megoura viciae producing a score of7/12 at 50 ppm: 11, 58, 71, 72, 73, 74, 75

According to the above method an application of the following compoundswas effective against the larvae of Phaedon cochleariae producing atleast 90% mortality at less than 5 ppm: 24, 29, 80, 89.

According to the above method an application of the following compoundswas effective against the larvae of Spodoptera littoralis producing atleast 70% mortality at less than 500 ppm: 28, 30.

The following Composition Examples illustrate compositions for useagainst arthropod, plant nematode, helminth or protozoan pests whichcomprise, as active ingredient, compounds of general formula I. Thecompositions described in Composition Examples 1 to 6 can each bediluted in water to give a sprayable composition at concentrationssuitable for use in the field.

COMPOSITION EXAMPLE 1

A water soluble concentrate was prepared from

    ______________________________________                                             5-Amino-3-cyano-1-(2,6-dichloro-4-                                                                 7%       w/v                                             trifluoromethylphenyl) -4-tri-                                                fluoromethylthiopyrazole                                                      Ethylan BCP          10%      w/v                                        and  N-methylpyrrolidone  to 100%  by volume                                  ______________________________________                                    

by dissolving the Ethylan BCP in a portion of N-methylpyrrolidone, andthen adding the active ingredient with heating and stirring untildissolved. The resulting solution was made up to volume by adding theremainder of the solvent.

COMPOSITION EXAMPLE 2

An emulsifiable concentrate was prepared from

    ______________________________________                                             5-Amino-3-cyano-1-(2,6-dichloro-                                                                   7%       w/v                                             4-trifluoromethylphenyl)-4-tri-                                               fluoromethylthiopyrazole                                                      Soprophor BSU        4%       w/v                                             Arylan CA            4%       w/v                                             N-methylpyrrolidone  50%      w/v                                        and  Solvesso 150         to 100%  by volume                                  ______________________________________                                    

by dissolving Soprophor BSU, Arylan CA and the active ingredient inN-methylpyrrolidone, and then adding Solvesso 150 to volume.

COMPOSITION EXAMPLE 3

A wettable powder was prepared from

                  ,                                                               ______________________________________                                             5-Amino-3-cyano-1-(2,6-                                                                            40%      w/w                                             dichloro-4-trifluoromethylphenyl)-                                            4-trifluoromethylthiopyrazole                                                 Arylan S             2%       w/w                                             Darvan No. 2         5%       w/w                                        and  Celite PF            to 100%  by weight                                  ______________________________________                                    

by mixing the ingredients, and grinding the mixture in a hammer-mill toa particle size less than 50 microns.

COMPOSITION EXAMPLE 4

An aqueous flowable formulation was prepared from

    ______________________________________                                               5-Amino-3-cyano-1-(2,6-                                                                         30%      w/v                                                dichloro-4-trifluoromethyl-                                                   phenyl)-4-trifluoromethyl-                                                    thiopyrazole                                                                  Ethylan BCP       1%       w/v                                                Sopropon T36      0.2%     w/v                                                Ethylene glycol   5%       w/v                                                Rhodigel 23       0.15%    w/v                                         and    Water             to 100%  by volume                                   ______________________________________                                    

by intimately mixing the ingredients and grinding in a bead mill untilthe median particle size was less than 3 microns.

COMPOSITION EXAMPLE 5

An emulsifiable suspension concentrate was prepared from

    ______________________________________                                               5-Amino-3-cyano-1-(2,6-                                                                         30%      w/v                                                dichloro-4-trifluoromethyl-                                                   phenyl)-4-trifluoromethyl-                                                    thiopyrazole                                                                  Ethylan BCP       10%      w/v                                                Bentone 38        0.5%     w/v                                         and    Solvesso 150      to 100%  by volume                                   ______________________________________                                    

by intimately mixing the ingredients and grinding in a bead mill untilthe median particle size was less than 3 microns.

COMPOSITION EXAMPLE 6

Water dispersible granules were prepared from

    ______________________________________                                               5-Amino-3-cyano-1-(2,6-                                                                         30%      w/w                                                dichloro-4-trifluoromethyl-                                                   phenyl)-4-trifluoromethyl-                                                    thiopyrazole                                                                  Darvan No. 2      15%      w/w                                                Arylan S          8%       w/w                                         and    Celite PF         to 100%  by weight                                   ______________________________________                                    

by mixing the ingredients, micronizing in a fluid-energy mill, and thengranulating in a rotating pelletiser by spraying on sufficient water (upto 10% w/w). The resulting granules were dried in a fluid-bed drier toremove excess water.

Descriptions of commercial ingredients used in the foregoing CompositionExamples:

    ______________________________________                                        Ethylan BCP  nonylphenol ethylene oxide condensate                            Soprophor BSU                                                                              condensate of tristyrylphenol and ethylene                                    oxide                                                            Arylan CA    70% w/v solution of calcium dodecylben-                                       zenesulphonate                                                   Solvesso 150 light C.sub.10 -aromatic solvent                                 Arylan S     sodium dodecylbenzenesulphonate                                  Darvan       sodium lignosulphonate                                           Celite PF    synthetic magnesium silicate carrier                             Sopropon T36 sodium salt of polycarboxylic acid                               Rhodigel 23  polysaccharide xanthan gum                                       Bentone 38   organic derivative of magnesium                                               montmorillonite                                                  ______________________________________                                    

COMPOSITION EXAMPLE 7

A dusting powder may be prepared by intimately mixing:

    ______________________________________                                        5-Amino-3-cyano-1-(2,6-dichloro-4-                                                                  1 to 10% w/w                                            trifluoromethylphenyl)-4-tri-                                                                       (weight/weight)                                         fluoromethylthiopyrazole                                                      Talc superfine        to 100% by weight                                       ______________________________________                                    

This powder may be applied to a locus of arthropod infestation, forexample refuse tips or dumps, stored products or household goods oranimals infested by, or at risk of infestation by, arthropods to controlthe arthropods by oral ingestion. Suitable means for distributing thedusting powder to the locus of arthropod infestation include mechanicalblowers, handshakers and livestock self treatment devices.

COMPOSITION EXAMPLE 8

An edible bait may be prepared by intimately mixing:

    ______________________________________                                        5-Amino-3-cyano-1-(2,6-dichloro-                                                                    0.1 to 1.0%                                                                             w/w                                           4-trifluoromethylphenyl)-4-tri-                                               fluoromethylthiopyrazole                                                      Wheat flour           80%       w/w                                           Molasses              to 100%   w/w                                           ______________________________________                                    

This edible bait may be distributed at a locus, for example domestic andindustrial premises, e.g. kitchens, hospitals or stores, or outdoorareas, infested by arthropods, for example ants, locusts, cockroachesand flies, to control the arthropods by oral ingestion.

COMPOSITION EXAMPLE 9

A solution may be prepared containing:

    ______________________________________                                        5-Amino-3-cyano-1-(2,6-                                                                           15% w/v                                                                       (weight/volume)                                           dichloro-4-trifluoromethyl-                                                   phenyl)-4-trifluoromethyl-                                                    thiopyrazole                                                                  Dimethylsulphoxide  to 100% by volume                                         ______________________________________                                    

by dissolving the pyrazole derivative in a portion of thedimethyl-sulphoxide and then adding more dimethylsulphoxide to thedesired volume. This solution may be applied to domestic animalsinfested by arthropods, percutaneously as a pour-on application or,after sterilisation by filtration through a polytetrafluoroethylenemembrane (0.22 micrometer pore size), by parenteral injection, at a rateof application of from 1.2 to 12 ml of solution per 100 kg of animalbody weight.

COMPOSITION EXAMPLE 10

A wettable powder may be formed from:

    ______________________________________                                        5-Amino-3-cyano-1-(2,6-dichloro-4-                                                                   50% w/w                                                trifluoromethylphenyl)-4-tri-                                                 fluoromethylthiopyrazole                                                      Ethylan BCP (a nonylphenol/ethylene                                                                   5% w/w                                                oxide condensate containing 9 moles                                           of ethylene oxide per mol of phenol)                                          Aerosil (silicon dioxide of                                                                           5% w/w                                                microfine-particle size)                                                      Celite PF (synthetic magnesium                                                                       40% w/w                                                silicate carrier)                                                             ______________________________________                                    

by adsorbing the Ethylan BCP onto the Aerosil, mixing with the otheringredients and grinding the mixture in a hammer-mill to give a wettablepowder, which may be diluted with water to a concentration of from0.001% to 2% w/v of the pyrazole compound and applied to a locus ofinfestation by arthropods, for example dipterous larvae, or plantnematodes by spraying, or to domestic animals infested by, or at risk ofinfestation by, arthropods, helminths or protozoa, by spraying ordipping, or by oral administration in drinking water, to control thearthropods, helminths or protozoa.

COMPOSITION EXAMPLE 11

A slow release bolus may be formed from granules containing a densityagent, binder, slow-release agent and5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazolecompound at varying percentage compositions. By compressing the mixturea bolus with a specific gravity of 2 or more can be formed and may beadministered orally to ruminant domestic animals for retention withinthe reticulo-rumen to give a continual slow release of pyrazole compoundover an extended period of time to control infestation of the ruminantdomestic animals by arthropods, helminths or protozoa.

COMPOSITION EXAMPLE 12

A slow release composition may be prepared from:

    ______________________________________                                        5-Amino-3-cyano-1-(2,6-dichloro-                                                                    0.5 to 25%                                                                              w/w                                           4-trifluoromethylphenyl)-4-tri-                                               fluoromethylthiopyrazole                                                      polyvinylchloride base                                                                              to 100%   w/w                                           ______________________________________                                    

by blending the polyvinylchloride base with the pyrazole compound and asuitable plasticiser, e.g. dioctyl phthalate, and melt-extruding orhot-moulding the homogenous composition into suitable shapes, e.g.granules, pellets, brickettes or strips, suitable, for example, foraddition to standing water or, in the case of strips, fabrication intocollars or ear-tags for attachment to domestic animals, to controlinsect pests by slow release of the pyrazole compound.

Similar compositions may be prepared by replacing the5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazolein the Composition Examples by the appropriate quantity of any othercompound of general formula I.

In experiments on activity against arthropods carried out onrepresentative compounds of the second embodiment, the following resultshave been obtained:

Test 2

One or more of the dilutions of the compounds to be tested were made in50% aqueous acetone. Test species: Spodoptera littoralis (Egyptiancotton worm).

French bean leaf discs were set in agar in petri dishes and infectedwith 5 2nd instar larvae. Four replicate dishes were assigned to eachtreatment and were sprayed under a Potter Tower with the appropriatetest dilution. After 2 days, live larvae were transferred to similardishes containing untreated leaves set in agar. Two or three days later,the dishes were removed from the constant temperature (25° C.) room inwhich they had been held and the mean percentage mortalities of larvaewere determined. These data were corrected against the mortalities indishes treated with 50% aqueous acetone alone which served as controls.

According to the above method an application of 500 ppm of the followingcompounds was effective against the larvae of Spodoptera littoralis,producing at least 70% mortality: Compounds 102, 103, 104, 105, 106,107.

The following Composition Examples illustrate compositions for useagainst arthropod, plant nematode, helminth or protozoan pests whichcomprise, as active ingredients, compounds of formula XXVI. Thecompositions described in Composition Examples 13 to 18 can each bediluted in water to give a sprayable composition at concentrationssuitable for use in the field.

COMPOSITION EXAMPLE 13

A water-soluble concentrate was prepared from

    ______________________________________                                             5-Acetamido-3-cyano-1-(2,6-dichlor-                                                                7%       w/v                                             o-4-trifluoromethylphenyl)-4-                                                 nitropyrazole                                                                 Ethylan BCP          10%      w/v                                        and  N-methylpyrrolidone  to 100%  by volume                                  ______________________________________                                    

by dissolving the Ethylan BCP in a portion of N-methylpyrrolidone, andthen adding the active ingredient with heating and stirring untildissolved. The resulting solution was made up to volume by adding theremainder of the solvent.

COMPOSITION EXAMPLE 14

An emulsifiable concentrate was prepared from

    ______________________________________                                             5-Acetamido-3-cyano-1-(2,6-dichlor-                                                                7%       w/v                                        o-4-trifluoromethylphenyl)-4-                                                      nitropyrazole                                                                 Soprophor BSU        4%       w/v                                             Arylan CA            4%       w/v                                             N-methylpyrrolidone  50%      w/v                                        and  Solvesso 150         to 100%  by volume                                  ______________________________________                                    

by dissolving Soprophor BSU, Arylan CA and the active ingredient inN-methylpyrrolidone, and then adding Solvesso 150 to volume.

COMPOSITION EXAMPLE 15

A wettable powder was prepared from

    ______________________________________                                             5-Acetamido-3-cyano-1-(2,6-dichlor-                                                                40%      w/w                                             o-4-trifluoromethylphenyl)-4-nitro                                            pyrazole                                                                      Arylan S             2%       w/w                                             Darvan No. 2         5%       w/w                                        and  Celite PF            to 100%  by weight                                  ______________________________________                                    

by mixing the ingredients, and grinding the mixture in a hammer-mill toa particle size less than 50 microns.

COMPOSITION EXAMPLE 16

An aqueous flowable formulation was prepared from

    ______________________________________                                             5-Acetamido-3-cyano-1-(2,6-dichlor-                                                                30%      w/v                                             o-4-trifluoromethylphenyl)-4-                                                 nitropyrazole                                                                 Ethylan BCP          1%       w/v                                             Sopropon T36         0.2%     w/v                                             Ethylene glycol      5%       w/v                                             Rhodigel 23          0.15%    w/v                                        and  Water                to 100%  by volume                                  ______________________________________                                    

by intimately mixing the ingredients and grinding in a bead mill untilthe median particle size was less than 3 microns.

COMPOSITION EXAMPLE 17

An emulsifiable suspension concentrate was prepared from

    ______________________________________                                             5-Acetamido-3-cyano-1-(2,6-dichlor-                                                                30%      w/v                                             o-4-trifluoromethylphenyl)-4-                                                 nitropyrazole                                                                 Ethylan BCP          10%      w/v                                             Bentone 38           0.5%     w/v                                        and  Solvesso 150         to 100%  by volume                                  ______________________________________                                    

by intimately mixing the ingredients and grinding in a bead mill untilthe medium particle size was less than 3 microns.

COMPOSITION EXAMPLE 18

Water-dispersible granules were prepared from

    ______________________________________                                        5-Acetamido-3-cyano-1-(2,6-dichloro-                                                                 30%      w/w                                           4-trifluoromethylphenyl)-4-nitropyrazole                                      Darvan No. 2           15%      w/w                                           Arylan S               8%       w/w                                           and Celite PF          to 100% by weight                                      ______________________________________                                    

by mixing the ingredients, micronizing in a fluid-energy mill, and thengranulating in a rotating pelletizer by spraying on sufficient water (upto 10% w/w). The resulting granules were dried in a fluid-bed drier toremove excess water.

Descriptions of Commercial Ingredients used in the Foregoing CompositionExamples

Ethylan BCP nonylphenol ethylene oxide condensate

    ______________________________________                                        Soprophor BSU                                                                            condensate of tristyrylphenol and ethylene                                    oxide                                                              Arylan CA  70% w/v solution of calcium dodecylben-                                       zenesulphonate                                                     Solvesso 150                                                                             light C.sub.10 -aromatic solvent                                   Arylan S   sodium dodecylbenzenesulphonate                                    Darvan     sodium lignosulphonate                                             Celite PF  synthetic magnesium silicate carrier                               Sopropon T36                                                                             sodium salt of polycarboxylic acid                                 Rhodigel 23                                                                              polysaccharide xanthan gum                                         Bentone 38 organic derivative of magnesium montmoril-                                    lonite                                                             ______________________________________                                    

COMPOSITION EXAMPLE 19

A dusting powder may be prepared by intimately mixing:

    ______________________________________                                        5-Acetamido-3-cyano-1-(2,6-dichloro-                                                                1 to 10% w/w                                            4-trifluoromethylphenyl)-4-nitro-                                             pyrazole                                                                      Talc superfine        to 100% by weight                                       ______________________________________                                    

This powder may be applied to a locus of arthropod infestation, forexample refuse tips or dumps, stored products or household goods oranimals infested by, or at risk of infestation by arthropods to controlthe arthropods by oral ingestion. Suitable means for distributing thedusting powder to the locus of arthropod infestation include mechanicalblowers, handshakers and livestock self treatment devices.

COMPOSITION EXAMPLE 20

An edible bait may be prepared by intimately mixing:

    ______________________________________                                        5-Acetamido-3-cyano-1-(2,6-dichloro-                                                                0.1 to 1.0%                                                                              w/w                                          4-trifluoromethylphenyl)-4-nitro-                                             pyrazole                                                                      Wheat flour           80%        w/w                                          Molasses              to 100%    w/w                                          ______________________________________                                    

This edible bait may be distributed at a locus, for example domestic andindustrial premises, e.g. kitchens, hospitals or stores, or outdoorareas, infested by arthropods, for example ants, locusts, cockroachesand flies, to control the arthropods by oral ingestion.

COMPOSITION EXAMPLE 21

A solution may be prepared containing:

    ______________________________________                                        5-Acetamido-3-cyano-1-(2,6-                                                                         15% w/v                                                 dichloro-4-trifluoromethylphenyl)-                                                                  (weight/volume)                                         4-nitropyrazole                                                               Dimethylsulphoxide    to 100% by volume                                       ______________________________________                                    

by dissolving the pyrazole derivative in a portion of thedimethylsulphoxide and then adding more dimethylsulphoxide to thedesired volume.

This solution may be applied to domestic animals infested by arthropods,percutaneously as a pour-on application or, after sterilization byfiltration through a polytetrafluoroethylene membrane (0.22 micrometerpore size), by parenteral injection, at a rate of application of from1.2 to 12 ml of solution per 100 kg of animal body weight.

COMPOSITION EXAMPLE 22

A wettable powder may be formed from:

    ______________________________________                                        5-Acetamido-3-cyano-1-(2,6-dichloro-4-                                                                 50%     w/w                                          trifluoromethylphenyl)-4-nitropyrazole                                        Ethylan BCP (a nonylphenol/ethylene oxide                                                              5%      w/w                                          condensate containing 9 moles of ethylene                                     oxide per mole of phenol)                                                     Aerosil (silicon dioxide of microfine-                                                                 5%      w/w                                          particle size)                                                                Celite PF (synthetic magnesium silicate                                                                40%     w/w                                          Carrier)                                                                      ______________________________________                                    

by adsorbing the Ethylan BCP onto the Aerosil, mixing with the otheringredients and grinding the mixture in a hammer-mill to give a wettablepowder, which may be diluted with water to a concentration of from0.001% to 2% w/v of the pyrazole compound and applied to a locus ofinfestation by arthropods, for example dipterous larvae, or plantnematodes by spraying, or to domestic animals infested by, or at risk ofinfestation by, arthropods, helminths or protozoa, by spraying ordipping, or by oral administration as drinking water, to control thearthropods, helminths or protozoa.

COMPOSITION EXAMPLE 23

A slow release bolus may be formed from granules containing a densityagent, binder, slow-release agent and5-acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazolecompound at varying percentage compositions. By compressing the mixture,a bolus with a specific gravity of 2 or more can be formed and may beadministered orally to ruminant domestic animals for retention withinthe reticulo-rumen to give a continual slow release of pyrazole compoundover an extended period of time to control infestation of the ruminantdomestic animals by arthropods, helminths or protozoa.

COMPOSITION EXAMPLE 24

A slow release composition may be prepared from:

    ______________________________________                                        5-Acetamido-3-cyano-1-(2,6-                                                                        0.5 to 25% w/w                                           dichloro-4-trifluoramethylphenyl)-                                            4-nitropyrazole                                                               polyvinylchloride base                                                                             to 100%    w/w                                           ______________________________________                                    

by blending the polyvinylchloride base with the pyrazole compound and asuitable plasticizer, e.g. dioctyl phthalate, and melt-extruding orhot-moulding the homogenous composition into suitable shapes, e.g.granules, pellets, brickettes or strips, suitable, for example, foraddition to standing water or, in the case of strips, fabrication intocollars or ear-tags for attachment to domestic animals, to controlinsect pests by slow release of the pyrazole compound.

Similar compositions may be prepared by replacing the5-acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazolein the Composition Examples by the appropriate quantity of any othercompound of general formula XXVI.

In the third preferred embodiment, the present invention provides anarthropodical, plant nematocidal or anthelmintic composition whichcomprises at least one compound of formula I, or at salt thereof, inassociation with one or more compatible diluents or carriers with theprovisos that (1) when the composition comprises a single compound ofgeneral formula I wherein R¹ and R³ both represent methyl, R² representsthiocyanato and R⁴ -R⁸ represent 2-, 3- or 4-nitro, 4-methyl, 4-chloroor 2,4-dinitro substitution; or R¹ represents methyl, R² representscyano, R³ represents unsubstituted amino and R⁴ -R⁸ represent 4-chloro,2,4-dichloro, 3,4-dichloro, 3-chloro-4-methyl or 2-methyl-4-chlorosubstitution, the composition is not an association of a single compoundof formula (I) alone with water or a common organic solvent; (2) whenthe composition comprises a single compound of general formula I whereinR¹ represents methyl, R² represents cyano or CONH₂, R³ representsunsubstituted amino and R⁴ -R⁸ represent 3- or 4-fluoro substitution; orR¹ represents ethyl, R² represents cyano or CONH₂, R³ representsunsubstituted amino and R⁴ -R⁸ represent 3- or 4-chloro, 2-, 3- or4-fluoro or methyl, 3-bromo or 3-nitro substitution; or R¹ representspropyl, R² represents cyano or CONH₂, R³ represents unsubstituted aminoand R⁴ -R⁸ represent 3-fluoro substitution; or R¹ represents methyl, R²represents sulphamoyl, R³ represents chloro and R⁴ -R⁸ represent4-chloro substitution; the composition comprises an agriculturallyacceptable surface active agent or a feedstuff; (3) when R¹ representsmethyl, R² represents nitro, and R³ represents chloro or R¹ representschloro, R² represents nitro, and R³ represents methyl and R⁴ -R⁸represents 4-nitro substitution, the composition comprises apharmaceutically acceptable adjuvant or a feedstuff or is substantiallysterile and pyrogen-free or is in unit dosage form; and (4) excludingcompositions comprising1-(4-nitrophenyl)-3-nitro-4-pyrazole-carbonitrile or carboxamide.

Medicated feeds which comprise known compounds of general formula I andarthropodicidally- or anthelmintically-acceptable salts thereof and anedible carrier or diluent form a feature of the present invention.

In experiments on activity against arthropods carried out onrepresentative compounds, the following results (wherein "Dose mg/kg"indicates the dose of test compound administered in mg per kg animalbody weight and ppm indicates the concentration of the compound in partsper million of the test solution applied) have been obtained:

Test 3

One or more dilutions of the compounds to be tested were made in 50%aqueous acetone.

a) Test species: Plutella xylostella (Diamond-back Moth) and Phaedoncochleariae (Mustard Beetle)

Turnip leaf discs were set in agar in petri-dishes and infected with 10larvae (2nd instar Plutella or 3rd instar Phaedon). Four replicatedishes were assigned to each treatment and were sprayed under a PotterTower with the appropriate test dilution. Four or five days aftertreatment the dishes were removed from the constant temperature (25° C.)room in which they had been held and the mean percentage mortalities oflarvae were determined. These data were corrected against themortalities in dishes treated with 50% aqueous acetone alone whichserved as controls.

b) Megoura viciae (Vetch Aphid)

Potted tic bean plants previously infected with mixed stages of Megourawere sprayed to run-off using a laboratory turntable sprayer. Treatedplants were held in a greenhouse for 2 days and were assessed for aphidmortality using a scoring system, judging the response in comparisonwith plants treated with 50% aqueous acetone alone, as controls.

    ______________________________________                                        Score                                                                         3               all aphids dead                                               2               few aphids alive                                              1               most aphids alive                                             0               no significant mortality                                      ______________________________________                                    

According to the above method (a) an application of 500 ppm of thefollowing compounds was totally effective against the larvae of Plutellaxylostella, producing 100% mortality.

Compound Nos.

113, 114, 115, 116, 128, 129, 130, 136, 138, 139, 140, 143, 144, 145,146, 147, 149, 150, 151, 152, 176, 177, 178, 179, 180, 181, 184, 187,188, 189, 193, 195, 202, 207, 210, 211, 212, 213, 214, 216, 219, 228,229.

According to the above method (a) an application of 5 ppm of thefollowing compounds was totally effective against the larvae of Phaedoncochleariae, producing 100% mortality.

Compound Nos.

144, 161, 165, 166, 178, 179, 182, 187, 188, 193, 198, 199, 205, 206,207, 210, 212, 214, 216, 217, 219, 220, 221, 224, 226, 228, 229.

According to the above method (b) an application of 50 ppm of thefollowing compounds was totally effective against Megoura viciaeproducing 100% mortality, that is given a score of 12 from 4 replicates.

Compound Nos.

112, 113, 128, 129, 144, 156, 161, 165, 166, 190, 191, 200, 201, 206,210, 214, 217, 219, 224, 225, 226, 228.

The data quoted in Tables 1-3 summarize the results from a number ofdifferent experiments carried out to the protocols a) and b) above.

                  TABLE 1                                                         ______________________________________                                               Plutella    Phaedon    Megoura                                         No.    % m 500 ppm % m 10 ppm score/12 50 ppm                                 ______________________________________                                        113                100                                                        114                100         9                                              115                100        10                                              127    100*        100        10                                              128                100                                                        129                100                                                        150                100        10                                              118     73          45        10                                              151                100        11                                              ______________________________________                                    

                  TABLE 2                                                         ______________________________________                                                    Plutella   Phaedon                                                No.         % m 500 ppm                                                                              % m 10 ppm                                             ______________________________________                                        116                     93                                                    110         89         100                                                    155         96         100                                                    143                    100                                                    130                    100                                                    131         58         100                                                    132         10         100                                                    138                    100                                                    136                     56                                                    137         48         100                                                    133          21*       100                                                    139                     16                                                    146                     85                                                    149                    100                                                    145                    100                                                    141         44         100                                                    152                    100                                                    140                     84                                                    148         98          21                                                    147                    100                                                    ______________________________________                                    

                  TABLE 3                                                         ______________________________________                                                    Phaedon    Megoura                                                No.         % m 10 ppm score/12 50 ppm                                        ______________________________________                                        112         98                                                                153         100        11                                                     117         68         10+                                                    ______________________________________                                         *% mortality at 100 ppm                                                       +score at 10 ppm                                                         

Test 4

Some 20 larvae of Rhipicephalus appendiculatus were placed in plasticcapsules attached to the shaved flank of guinea-pigs. After 3 hours andthen at 23 hourly intervals, the guinea-pigs were given a total of 4subcutaneous injections of the test compound. Approximately 100 hoursafter infestation, the guinea-pigs were killed and the engorged ticklarvae recovered, counter and kept at 23° C. in a humidity cabinet for14 to 21 days. After this period, the percentage survival throughmoulting was assessed. Results obtained are given below in Table 4.

                  TABLE 4                                                         ______________________________________                                                  Dose (mg/kg                                                         Compound  at each                                                             No.       repetition) Result                                                  ______________________________________                                        120       5           No ticks recovered                                                4           No ticks recovered                                                3           Less than five engorged ticks                                                 recovered                                                         2.5         Ticks engorged normally but                                                   only 62.5 percent survived                              113       5           No ticks recovered                                                4           No ticks recovered                                                3           Number of engorged ticks                                                      reduced, only 8.3 percent                                                     survived                                                          2.5         Ticks engorged normally but                                                   only 30.0 percent survived                                        1.0         Ticks engorged normally but                                                   only 47.9 percent survived                              134       10          No ticks recovered                                                5           Less than five engorged ticks                                                 recovered                                               133       15          No ticks recovered                                                5           No ticks recovered                                                2.5         No ticks recovered                                      ______________________________________                                    

Test 5

The high activity of the compounds of the third embodiment of generalformula I against the cockroach species Periplaneta americana isdemonstrated by results from the following experiment.

0.2 microliters of an acetone solution of the compound was injectedthrough the soft cuticle between the leg and thorax of ten insects, togive a dose rate of 5 micrograms per g of insect body weight. Tencockroaches were similarily injected with 0.2 microliters of acetonealone to serve as controls. After treatment the insects were held inplastic boxes with appropriate food. Five days after treatment thenumbers of dead and alive insects were counted and percentagemortalities calculated.

According to the above method a dose of 5 micrograms/g insect bodyweight of the following compounds was totally effective against thecockroach species Periplaneta americana producing 100% mortality.

Compound Nos.

110, 113, 122, 125, 130, 161

The following Examples illustrate compositions for use againstarthropod, plant nematode or helminth pests which comprise, as activeingredients, compounds of general formula I.

COMPOSITION EXAMPLE 25

A dusting powder may be prepared by intimately mixing:

    ______________________________________                                        5-amino-4-cyano-1-(2,6-dichloro-4-                                                                  1 to 10% w/w                                            trifluoromethylphenyl)-                                                                             (weight/weight)                                         3-trifluoromethylpyrazole                                                     Talc superfine        to 100% by weight                                       ______________________________________                                    

This powder may be applied to a locus of arthropod infestation, forexample refuse tips or dumps, stored products or household goods oranimals infested by, or at risk of infestation by, arthropods to controlthe arthropods by oral ingestion. Suitable means for distributing thedusting powder to the locus of arthropod infestation include mechanicalblowers, handshakers and livestock self treatment devices.

The5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolemay, if desired, be replaced in the above dusting powder by any othercompound of general formula I.

COMPOSITION EXAMPLE 26

An edible bait may be prepared by intimately mixing:

    ______________________________________                                        5-amino-4-cyano-1-(2,6-dichloro-4-                                                                 0.1 to 1.0%                                                                              w/w                                           trifluoromethylphenyl)-                                                       3-trifluoromethylpyrazole                                                     Wheat flour          80%        w/w                                           Molasses             to 100%    w/w                                           ______________________________________                                    

This edible bait may be distributed at a locus, for example domestic andindustrial premises, e.g. kitchens, hospitals or stores, or outdoorareas, infested by arthropods, for example ants, locusts, cockroachesand flies, to control the arthropods by oral ingestion.

The5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolemay, if desired, be replaced in the above edible bait by any othercompound of the third embodiment of general formula I.

COMPOSITION EXAMPLE 27

A solution may be prepared containing:

    ______________________________________                                        5-amino-4-cyano-1-(2,6-dichloro-4-                                                               15% w/w(weight/volume)                                     trifluoromethylphenyl)-                                                       3-trifluoromethylpyrazole                                                     Dimethylsulphoxide to 100% by volume                                          ______________________________________                                    

by dissolving the pyrazole derivative in a portion of thedimethylsulphoxide and then adding more dimethylsulphoxide to thedesired volume. This solution may be applied to domestic animals infesedby arthropods, percutaneously as a pour-on application or, aftersterilization by filtration through a polytetrafluoroethylene membrane(0.22 um pore size), by parenteral injection, at a rate of applicationof from 1.2 to 12 ml of solution per 100 kg of animal body weight.

The5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolemay, if desired, be replaced in the above solution by similar amounts ofan other compound of the third embodiment of general formula I.

COMPOSITION EXAMPLE 28

A wettable powder may be formed from:

    ______________________________________                                        5-amino-4-cyano-1-(2,6-dichloro-4-                                                                     50%     w/w                                          trifluoromethylphenyl)-                                                       3-trifluoromethylpyrazole                                                     Ethylan BCP (a nonylphenol/ethylene oxide                                                              5%      w/w                                          condensate containing 9 moles of                                              ethylene oxide per mole of phenol)                                            Aerosil (silicon dioxide of microfine-                                                                 5%      w/w                                          particle size)                                                                Celite PF (synthetic magnesium                                                                         40%     w/w                                          silicate carrier)                                                             ______________________________________                                    

by adsorbing the Ethylan BCP onto the Aerosil, mixing with the otheringredients and grinding the mixture in a hammer-mill to give a wettablepowder, which may be diluted with water to a concentration of from0.001% to 2% w/v of the pyrazole compound and applied to a locus ofinfestation by arthropods, for example dipterous larvae, or plantnematodes by spraying, or to domestic animals infested by, or at risk ofinfestation by, arthropods, by spraying or dipping, or by oraladministration as drinking water, to control the arthropods orhelminths.

The5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolemay, if desired, be replaced in the above wettable powder by any othercompound of the third embodiment of general formula I.

COMPOSITION EXAMPLE 29

A slow release bolus may be formed from granules containing a densityagent, binder, slow-release agent and5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolecompound at varying percentage compositions. By compressing the mixturea bolus with a specific gravity of 2 or more can be formed and may beadministered orally to ruminant domestic animals for retention withinthe reticulo-rumen to give a continual slow release of pyrazole compoundover an extended period of time to control infestation of the ruminantdomestic animals by arthropods or helminths.

The5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolemay, if desired, be replaced in the above bolus by any other compound ofthe third embodiment of general formula I.

COMPOSITION EXAMPLE 30

A slow release composition may be prepared from:

    ______________________________________                                        5-amino-4-cyano-1-(2,6-dichloro-4-                                                                 0.5 to 25% w/w                                           trifluoromethylphenyl)-                                                       3-trifluoromethylpyrazole                                                     polyvinylchloride base                                                                             to 100%    w/w                                           ______________________________________                                    

by blending the polyvinylchloride base with the pyrazole compound and asuitable plasticizer, e.g. dioctyl phthalate, and melt-extruding orhot-moulding the homogeneous composition into suitable shapes, e.g.granules, pellets, brickettes or strips, suitable, for example, foraddition to standing water or, in the case of strips, fabrication intocollars or ear-tags for attachment to domestic animals, to controlinsect pests by slow release of the pyrazole compound.

The compounds of general formula I can be prepared by the application oradaptation of known methods (i.e. methods heretofore used or describedin the chemical literature), generally heterocycle (pyrazole ring)formation followed where necessary by changing substituents.

It is to be understood that in the description of the followingprocesses that the sequences for the introduction of the various groupson the pyrazole ring may be performed in a different order and thatsuitable protecting groups may be required as will be apparent to thoseskilled in the art: compounds of general formula I may be convened byknown methods into other compounds of general formula I.

In the following description when symbols appearing in formulae are notspecifically defined it is to be understood that they are "ashereinbefore defined" in accordance with the first definition of eachsymbol in this specification. Within the process definitions, unlessotherwise stated, amino refers to the unsubstituted amino group.

Compounds of the first embodiment of the invention corresponding togeneral formula I wherein R² represents an R'SO₂, R'SO or R'S group, R³represents the unsubstituted amino group and R¹ represents the cyano oracetyl group may be prepared by a process version "a" in which acompound of formula II wherein R⁹ represents a cyano or acetyl group isreacted with a compound of formula R² CH₂ CN, preferably a molarequivalent thereof, generally in the presence of an anhydrous inertorganic solvent, e.g. ethanol, and a molar equivalent of a base, e.g.sodium ethoxide, and at a temperature from 0° to 50° C.

Compounds of general formula I wherein R² represents an R'S group and R³represents an amino group --NR"R"' wherein R" and R"' each represent ahydrogen atom or a straight or branched chain alkyl, alkenylalkyl oralkynylalkyl group as hereinbefore defined may be prepared by a processversion "b" in which an intermediate corresponding to general formula Iin which R² is replaced by the hydrogen atom is reacted with a compoundof formula:

    R'--SCl                                                    (III)

(wherein R' is as hereinbefore defined) in an inert organic solvent,preferably chloroform or dichloromethane, optionally in the presence ofa base, preferably pyridine, and at temperatures from 0° to 50° C.

Compounds of general formula I wherein R¹ represents a chlorine orfluorine atom, R² represents an R'SO₂, R'SO or R'S group, and R³represents an amino group may be prepared by a process version "c" inwhich a compound of formula IV wherein X and Y both represent chlorineatoms or both represent fluorine atoms, is reacted with aphenylhydrazine of formula V: ##STR2## or an acid addition salt thereof,e.g. the hydrochloride, in an inert solvent, preferably ether ortetrahydrofuran, and optionally in the presence of a base, e.g.triethylamine or sodium acetate, and at a temperature from 0° C. to thereflux temperature of the solvent. When an acid addition salt of thecompound of formula (V) is used, the reaction with the compound offormula (IV) is effected in the presence of an alkali metal, e.g. sodiumor potassium, acetate, carbonate or bicarbonate.

According to a further process version "d" (1), compounds of generalformula I wherein R² represents an R'S group, R¹ represents a chlorine,bromine, iodine or fluorine atom or a cyano or nitro group, and R³represents an amino group may also be prepared by the reaction ofcorresponding 4-thiocyanatopyrazoles with an organometallic reagent suchas a compound of formula VI:

    R'--Mg--X.sup.1                                            (VI)

wherein R' is as hereinbefore defined and X¹ represents a halogen atomin an inert solvent, such as diethyl ether ortetrahydrofuran, and at atemperature from -78° C. to the reflux temperature of the reactionmixture or a compound of formula IX:

    R.sup.10 --C≡C.sup.- Li.sup.+                        (IX)

wherein R¹⁰ --C≡C⁻ corresponds to R' in (I), in an inert solvent, suchas tetrahydrofuran or diethyl ether, at temperatures from -78° C. toambient.

Alternatively, according to process version "d" (2), compounds ofgeneral formula I in which R² represents an R'S group wherein R'S isother than a 1-alkenylthio or 1-alkynylthio group may also be preparedby reacting an intermediate corresponding to general formula I in whichR² is replaced by a thiocyanato group, with a base preferably sodiumhydroxide, or a reducing agent preferably sodium borohydride, in thepresence of a reagent of formula VII:

    R'.sup.a --X.sup.2                                         (VII)

wherein R'^(a) is as hereinbefore defined for R' with the exclusion of1-alkenyl and 1-alkynyl and X² represents a halogen, preferably bromineor iodine, for example methyl iodide or propargyl bromide, or with abase preferably sodium hydroxide, in the presence of a reagent offormula VIIA:

    F.sub.2 C═C(Z)Z'                                       (VIIA)

wherein Z represents a fluorine, chlorine or bromine atom and Z' is ashereinbefore defined for Z or represents the trifluoromethyl group in aninert organic or aqueous-organic solvent, such as methanol, ethanol ordioxan or mixtures of these solvents with water, the reaction beingperformed at a temperature from -40° C. to the reflux temperature.

Alternatively, according to process version "d" (3), compounds ofgeneral formula I wherein R'S is other than a 1-alkenylthio or1-alkynylthio group may be prepared by reductive alkylation ofdisulphides of formula VIII employing a reducing agent preferably sodiumdithionite or sodium borohydride, in the presence of a base, preferablysodium hydroxide or sodium carbonate, and of a halide of formula VII,such as methyl iodide, in an inert organic or aqueous-organic solventsuch as ethanol or a mixture of alcohol and water, at a temperature fromambient to reflux.

According to a further process version "e", compounds of general formulaI in which R² represents an R'SO or R'SO₂ -group may be prepared byoxidation of the sulphur atoms of the corresponding alkylthio,alkenylthio or alkynylthio compounds of formula (I) wherein R² is agroup R'S as defined above; the oxidation may be effected employingoxidants of formula (X):

    R.sup.11 --O--O--H                                         (X)

wherein R¹¹ represents the hydrogen atom, or a trifluoroacetyl orpreferably 3-chlorobenzoyl group in a solvent e.g. dichloromethane orchloroform or trifluoroacetic acid and at temperatures from 0° C. to 60°C., or with a reagent such as potassium hydrogen persulphate orpotassium salt of Caro's acid in a solvent e.g. methanol and water, andat a temperature from -30° C. to 50° C.

According to a further process version "f" (1), compounds of generalformula I wherein R¹ represents a chlorine, bromine or iodine atom or acyano or nitro group may be prepared by the diazotisation of anintermediate corresponding to general formula I in which R¹ is replacedby the amino group and R³ represents a hydrogen atom or the amino groupusing sodium nitrite in a mineral acid, for example a mixture ofconcentrated sulphuric acid and acetic acid, at a temperature from 0° to60° C., and by subsequent reaction with a copper salt and a mineral acidor with an aqueous solution of potassium iodide (when R¹ represents aniodine atom) at a temperature from 0° to 100° C.; or with cuprouscyanide, or sodium nitrite in the presence of a copper salt in an inertsolvent e.g. water at pH from 1 to 7 at 25° to 100° C. The diazotisationmay alternatively be performed employing an alkyl nitrite e.g.tert-butyl nitrite in the presence of a suitable halogenating agentpreferably bromoform or iodine or anhydrous cupric chloride attemperatures from 0° C. to 100° C., and optionally in the presence of aninert solvent, preferably acetonitrile or chloroform.

According to a further process version "f" (2), compounds of formula Iwherein R¹ represents a fluorine atom and R³ represents a hydrogen atomor the amino group may be prepared by diazotisation of the correspondingamine wherein R¹ is replaced by the amino group using for example asolution of sodium nitrite in sulphuric acid and in the presence offluoroboric acid or its sodium salt and subsequent thermolysis orphotolysis of the diazonium fluoroborate derivative by methods known perse.

According to a further process version "g", compounds of formula Iwherein R¹ represents a fluorine atom or a cyano group, and R³represents a hydrogen atom or the amino group may be prepared by thereaction of a halide of formula I wherein R¹ represents a chlorine orbromine atom with an alkali metal fluoride, preferably cesium fluoride,or with a metal cyanide preferably KCN under anhydrous conditions in aninert solvent, preferably sulpholane, and at a temperature from ambientto 150° C.

According to a further process version "h", compounds of formula Iwherein R¹ represents a nitro group, and R² is a group R'SO₂ or R'SO maybe prepared by the reaction of an intermediate corresponding to generalformula I in which R¹ is replaced by an unsubstituted amino group, andR² is a group R'SO₂, R'SO or R'S, and R³ represents a hydrogen atom orthe amino group with an oxidant, preferably trifluoroperacetic acid orm-chloroperbenzoic acid, in an inert solvent, preferablydichloromethane, at a temperature from 0° C. to the reflux temperature.In this process concomitant oxidation at sulphur may occur when R² isR'S.

According to a further process version "i", compounds of general formulaI wherein R¹ represents the cyano group and R³ represents a hydrogenatom or the amino group may also be prepared by the dehydration of acompound corresponding to general formula I in which R¹ is replaced bythe carbamoyl group. The compound corresponding to general formula I inwhich R¹ is replaced by the carbamoyl group may be prepared by thereaction of a compound corresponding to general formula I in which R¹ isreplaced by the carboxy group with a chlorinating agent, preferablythionyl chloride at ambient to reflux temperature, followed by reactionof the intermediate acid chloride with ammonia to give an intermediateamide. The dehydration is generally effected by heating with adehydrating agent e.g. phosphorus pentoxide or preferably phosphorusoxychloride at a temperature from 50° C. to 250° C.

According to a further process version "j", compounds of general formulaI wherein R¹ is the acetyl group, and R³ represents a hydrogen atom orthe amino group may be prepared by the reaction of the correspondingnitrile of formula (I) wherein R¹ is the cyano group, or of esterswherein R¹ is replaced by an alkoxycarbonyl group or of carboxylic acidswherein R¹ is replaced by a carboxy group with methyl lithium in aninert solvent, e.g. toluene, and at temperatures from -78° C. toambient. Alternatively the nitrile of formula (I) wherein R¹ is thecyano group or ester wherein R¹ is replaced by an alkoxycarbonyl groupmay be reacted with a Grignard reagent CH₃ MgX³ wherein X³ represents ahalogen, preferably iodine atom, in an inert solvent, e.g. diethyl etheror tetrahydrofuran, and at a temperature from 0° C. to the refluxtemperature of the solvent.

According to a further process version "k", compounds of general formulaI wherein R¹ represents the acetyl group and R³ is as defined above mayalternatively be prepared by oxidation of alcohols corresponding togeneral formula I wherein R¹ is replaced by a 1-hydroxyethyl group, withan oxidant, preferably pyridinium chlorochromate, in an inert solvent,e.g. dichloromethane, and at a temperature from 0° C. to the refluxtemperature of the solvent.

According to a further process version "1", compounds of the generalformula I wherein R¹ represents a formyl group and R³ is as definedabove may be prepared by the reaction of the corresponding nitriles ofgeneral formula I wherein R¹ represents a cyano group with

(1) a suitable reducing agent preferably diisobutylaluminium hydride inan inert solvent, preferably tetrahydrofuran and at a temperature from-78° C. to the ambient temperature, followed by mild hydrolysis with anacid, e.g. dilute hydrochloric acid, at room temperature; or

(2) Raney nickel in formic acid preferably at the reflux temperature offormic acid.

Derivatives of the 5-amino group form a further feature of the presentinvention and are collectively referred to as process "m". Compounds ofgeneral formula I which conform to formula IA wherein R" represents anR¹² C(═O)-- group, wherein R¹² represents a straight or branched-chainalkyl or alkoxy group containing from 1 to 4 carbon atoms, and R"'represents a hydrogen atom or an R¹² C(═O)-- group which is identical tothe group R¹² C(═O)-- represented by R" or --NR"R"' represents a cyclicimide as hereinbefore defined, may be prepared by the reaction of acompound of general formula I wherein R³ represents the unsubstitutedamino group, or an alkali metal salt thereof, with a compound of formulaXI:

    R.sup.12 --CO--X.sup.4                                     (XI)

wherein X⁴ represents a chlorine or bromine atom, or with a compound offormula XII:

    (R.sup.12 --CO).sub.2 O                                    (XII)

or with a dicarboxylic acid derivative. The reaction may be conducted inthe absence or presence of an inert organic solvent, for exampleacetonitrile, tetrahydrofuran, a ketone, e.g. acetone, an aromatichydrocarbon, e.g. benzene or toluene, chloroform, dichloromethane ordimethylformamide, and optionally in the presence of an acid-bindingagent, for example pyridine, triethylamine or an alkali metal, e.g.sodium or potassium, carbonate or bicarbonate, at a temperature from 0°C. to the reflux temperature of the reaction medium, to give a compoundof formula IA wherein R" represents an R¹² C(═O)-- group wherein R¹² isas hereinbefore defined and R"' represents a hydrogen atom or an R¹²C(═O)-- group, depending upon the reaction conditions chosen and/or theuse of an excess of the compound of formula XI or XII, or --NR"R"'represents a cyclic imide as hereinbefore defined.

Compounds of formula IA wherein R" represents a formyl group and R"'represents a hydrogen atom or a formyl group, may be prepared by thereaction of a compound of general formula I, wherein R³ represents theunsubstituted amino group with formylacetic anhydride. Formylaceticanhydride may be prepared from formic acid and acetic anhydride and thereaction with the compound of general formula I may be conducted in theabsence or presence of an inert organic solvent, for example a ketone,e.g. acetone, or an aromatic hydrocarbon, e.g. benzene or toluene, andoptionally in the presence of an acid-binding agent, for examplepyridine, triethylamine or an alkali metal, e.g. sodium or potassium,carbonate or bicarbonate, at a temperature from 0° C. to the refluxtemperature of the reaction mixture, to give a compound of formula IAwherein R" represents a formyl group and R"' represents a hydrogen atomor a formyl group, depending upon the reaction conditions chosen and/orthe use of an excess of formylacetic anhydride.

Compounds of formula IA wherein R" represents a formyl group or a groupR¹² C(═O)-- and R"' represents a hydrogen atom may be prepared by theselective removal by hydrolysis of an R¹² C(═O)-- group or a formylgroup from a compound of formula IA wherein R" and R"' both represent IIa R¹² C(═O)-- group or a formyl group. Hydrolysis is effected under mildconditions, for example by treatment with an aqueous-ethanolic solutionor suspension of an alkali metal, e.g. sodium or potassium, bicarbonate,or with aqueous ammonia.

Compounds of formula IA wherein R" represents a straight orbranched-chain alkoxycarbonyl group containing from 2 to 5 carbon atomswhich is unsubstituted or substituted by one or more halogen atoms, andR"' represents a hydrogen atom may be prepared by the reaction of acompound of the formula IB wherein R¹³ represents an alkoxycarbonylgroup R¹⁴ C(═O), wherein R¹⁴ represents a straight or branched-chainalkoxy group containing from 1 to 4 carbon atoms (which is unsubstitutedor substituted by one or more halogen atoms) or a phenoxy group, with acompound of the formula XIII:

    R.sup.14 --H                                               (XIII)

(wherein R¹⁴ is as hereinbefore defined) to replace a first grouprepresented by the symbol R¹³ by a hydrogen atom, and to replace thesecond group represented by the symbol R¹³ by an alkoxycarbonyl groupwhen R¹³ represents a phenoxycarbonyl group, or, if desired, to replacethe second group represented by the symbol R¹³ by another alkoxycarbonylgroup when R¹³ in formula (IB) represents an alkoxycarbonyl group. Aswill be apparent to those skilled in the art, the desired compound offormula IA is obtained by selection of the appropriate compounds offormulae IB and XIII. The reaction may be effected in water or an inertaqueous-organic or organic solvent, for example an alkanol containing 1to 4 carbon atoms, e.g. ethanol, or an aromatic hydrocarbon, e.g.benzene or toluene, or which is preferably an excess of the compound offormula XIII, at a temperature from ambient temperature to the refluxtemperature of the reaction mixture and, if necessary, at elevatedpressure, and optionally in the presence of a base, for example analkali metal alkoxide, e.g. of the compound of formula XIII.

Compounds of formula IA wherein R" and R"', which may be the same ordifferent, each represents a formyl group or R¹² C(═O)-- group, may beprepared by the reaction of an alkali metal, e.g. sodium or potassium,derivative of a compound of formula IA wherein R" represents a group R¹²C(═O)-- as hereinbefore defined, or a formyl group, and R"' represents ahydrogen atom with formylacetic anhydride or a compound of formula XI.Reaction may be effected in an inert aprotic solvent, e.g.dimethylformamide, at a temperature from laboratory temperature to thereflux temperature of the reaction mixture.

Alkali metal derivatives of compounds of general formula I (wherein R³represents the unsubstituted amino group) or (IA) wherein R" representsa group R¹² CO and R"' represents a hydrogen atom may be prepared insitu by reaction with an alkali metal, e.g. sodium or potassium,hydride, in an inert aprotic solvent, e.g. dimethylformamide, at atemperature from laboratory temperature to the reflux temperature of thereaction mixture.

Compounds of formula IB wherein R¹³ represents a group R¹⁴ C(═O)--, maybe prepared as hereinbefore described. Intermediates of formula IBwherein R¹³ represents a phenoxycarbonyl group may be prepared by thereaction of a compound of general formula I (wherein R³ represents theunsubstituted amino group), with a compound of formula XIV:

    R.sup.15 --CO--X.sup.4                                     (XIV)

(wherein R¹⁵ represents a phenoxy group and X⁴ is as hereinbeforedefined, e.g. phenyl chloroformate, or with a compound of formula XV:

    (R.sup.15 --CO).sub.2 O                                    (XV)

(wherein R¹⁵ is as hereinbefore defined) using the reaction conditionshereinbefore described for the reaction of a compound of general formulaI with a compound of formula XI or XII.

Compounds of formula IA wherein R" represents a group R¹⁶ whichrepresents a straight or branched-chain alkyl, alkenylalkyl oralkynylalkyl group containing up to 5 carbon atoms and R"' represents ahydrogen atom may be prepared by the removal of the group R¹² C(═O)-- ofa compound of the formula IA, wherein R" represents a group R¹⁶ and R"'represents a group R¹² C(═O)--. Removal of the group R¹² C(═O)-- may beeffected by selective hydrolysis under mild conditions, for example bytreatment with an alkali metal, e.g. sodium or potassium, hydroxide inwater or an inert organic or aqueous- organic solvent, for example alower alkanol, e.g. methanol, or a mixture of water and lower alkanol,at a temperature from laboratory temperature up to the refluxtemperature of the reaction mixture.

Compounds of formula IA, wherein R" represents a group R¹⁶ and R"'represents a group R¹² C(═O)--, may be prepared:

(1) by reaction of a compound of formula IA wherein R" represents ahydrogen atom and R"' represents a group R¹² C(═O), or an alkali metal,e.g. sodium or potassium, derivative thereof, with a compound of theformula XVI:

    R.sup.16 --X.sup.5                                         (XVI)

wherein X⁵ represents a chlorine, bromine or iodine atom; the reactionmay be effected in an inert organic solvent, e.g. dichloromethane,tetrahydrofuran, or dimethylformamide, at a temperature from laboratorytemperature up to the reflux temperature of the reaction mixture and,when a compound of formula IA is used, in the presence of a base, e.g.,Triton B; or

(2) by reaction of a compound of formula IA wherein R" represents thehydrogen atom and R"' represents a group R¹⁶ with a compound of formulaXI or XII.

Compounds of general formula I wherein R³ represents an N-(alkyl,alkenylalkyl or alkynylalkyl)-N-formylamino group as hereinbeforedescribed may be prepared in a similar manner to the process justdescribed, where appropriate, formylacetic anhydride instead of acompound of formula XI or XII.

Compounds of formula IA wherein one or both of R" and R"' represents astraight or branched-chain alkyl, alkenylalkyl or alkynylalkyl groupcontaining up to 5 carbon atoms, groups represented by R" and R"' beingidentical, may be prepared by reaction of a compound of formula I,wherein R³ represents the unsubstituted amino group, or an alkali metal,e.g. sodium or potassium, derivative thereof, with a compound of formulaXVI, in the absence or presence of an inert organic solvent, for examplean aromatic hydrocarbon, e.g. benzene or toluene, chloroform,dichloromethane, tetrahydrofuran or dimethylformamide, and optionally inthe presence of an acid-binding agent, for example pyridine,triethylamine or an alkali metal, e.g. sodium or potassium, bicarbonate,at a temperature from 0° C. up to the reflux temperature of the reactionmixture.

According to a further process version "n", compounds of general formulaI wherein R³ represents a straight or branched-chainalkoxymethyleneamino group containing from 2 to 5 carbon atoms which maybe unsubstituted or substituted on methylene by a straight orbranched-chain alkyl group containing from 1 to 4 carbon atoms may beprepared by the reaction of a compound of general formula I (wherein R³represents the unsubstituted amino group) with a trisalkoxyalkane in thepresence of an acidic catalyst, e.g. p-toluenesulphonic acid, at atemperature from ambient temperature to the reflux temperature of thereaction mixture.

According to a further process version "o", compounds of general formulaI wherein R³ represents a group --NHCH₂ R¹⁷ wherein R¹⁷ represents thehydrogen atom or a straight or branched-chain alkyl group containingfrom 1 to 4 carbon atoms may be prepared by reaction of a compound ofgeneral formula I wherein R³ represents --N═C(OR¹⁸)R¹⁷ wherein R¹⁸represents a straight or branched-chain alkyl group containing from 1 to4 carbon atoms with a reducing agent, preferably sodium borohydride. Thereaction may be effected in an inert organic solvent, ethanol ormethanol being preferred, at a temperature from 0° C. to the refluxtemperature of the reaction mixture.

Compounds of general formula I, wherein R³ represents a halogen atom,may be prepared by diazotisation of the corresponding compound ofgeneral formula I wherein R³ represents the amino group, adopting theprocedure of process "f" used above to prepare compounds of generalformula I wherein R¹ represents a halogen atom. Fluorides of generalformula I wherein R³ represents a fluorine atom may also be prepared bya halogen exchange reaction of halides of general formula I wherein R³represents a chlorine or bromine atom, adopting the procedure of process"g" used above to prepare compounds (I) wherein R¹ represents a fluorineatom.

According to a further process version "p", compounds of general formulaI wherein R¹ represents the formyl, acetyl, cyano or nitro group, R² isas defined, and R³ represents a fluorine atom may be prepared by ahalogen exchange reaction with a compound of general formula I whereinR³ represents a chlorine or bromine atom by heating with an alkali metalfluoride preferably caesium fluoride in an inert solvent preferablysulpholane and at a temperature from 50° C. to 150° C.

According to a further process version "q", compounds of general formulaI wherein R³ represents a hydrogen atom may be prepared by treatment ofa compound of general formula I wherein R³ represents an amino group,with a diazotising agent preferably tertiary butyl nitrite in a solvent,preferably tetrahydrofuran, and at ambient to the reflux temperature.

According to a further process version "r", compounds of formula IAwherein R¹ represents a cyano or nitro group, R² is a group R'SO₂, R"and R"' each represents a straight or branched chain alkyl, alkenylalkylor alkynylalkyl group containing up to 5 carbon atoms and R"' may alsorepresents a hydrogen atom may be prepared by the reaction of a compoundof general formula I wherein R³ represents a halogen, preferablybromine, atom with the corresponding amine within formula R"R"'NH, ordimethylhydrazine when R" and R"' are both methyl, in an inert solventpreferably dioxan, tetrahydrofuran, N,N-dimethylformamide,dimethylsulphoxide or sulpholane and at a temperature from 25° to 100°C.

Intermediate compounds of formula II wherein the R⁹ group represents acyano or acetyl group may be prepared by diazotization of the aniline offormula IIA (wherein R⁴ -R⁸ are as hereinbefore defined) generally witha solution of a molar equivalent of sodium nitrite in a mineral acid,e.g. a mixture of concentrated sulphuric acid and acetic acid, at atemperature from 0° to 60° C., and then reacting with a compound offormula CH₃ COCH(Cl)CN [preparation described in J. Org. Chem 43 (20),3822 (1978)] or a compound of formula CH₃ COCH(Cl)COCH₃ in the presenceof an inert solvent, e.g. a mixture of water and ethanol, optionallybuffered, e.g. with excess sodium acetate, and at a temperature from 0°to 50° C.

Intermediates corresponding to general formula I in which R³ representsan amino group, R² is replaced by the hydrogen atom, and R¹ representsthe cyano group may be prepared by diazotisation of the aniline offormula IIA generally with a solution of a molar equivalent of sodiumnitrite in a mineral acid, e.g. a mixture of concentrated sulphuric acidand acetic acid, at a temperature from 0° to 60° C., and then reactingwith a compound of formula XVII:

    NC--CH.sub.2 --CH(CO--R.sup.19)CN                          (XVII)

wherein R¹⁹ represents an alkoxy group containing from 1 to 6 carbonatoms, preferably the ethoxy group, or a hydrogen atom in the presenceof an inert solvent e.g. a mixture of water and ethanol, and optionallybuffered, e.g. with sodium acetate, and at a temperature from 0° to 50°C. Subsequent mild hydrolysis with a base such as aqueous sodiumhydroxide, sodium carbonate or ammonia may be necessary to effect thecyclization.

Intermediates of formula XVII used above, in which R¹⁹ represents thehydrogen atom, may be employed as alkali metal enolate salts which areconverted into the aldehydes under the acidic conditions of the abovecoupling reaction.

Intermediates corresponding to general formula I in which R¹ is asdefined with the exclusion of the formyl group, R² is replaced by thehydrogen atom and R³ represents an amino group may be prepared bydecarboxylation of a compound corresponding to general formula I whereinR² is replaced by the carboxy group, generally performed by heating at atemperature from 100° C. to 250° C. optionally in the presence of aninert organic solvent, particularly N,N-dimethylaniline. Alternativelyintermediates corresponding to general formula I in which R² is replacedby a hydrogen atom, R¹ is as defined with the exclusion of the formylgroup, and R³ represents an amino group may be prepared directly fromesters corresponding to general formula I wherein R² represents a group--COOR in which R represents a straight or branched chain alkyl groupcontaining from 1 to 6 carbon atoms, by heating in an inert organicsolvent preferably acetic acid at a temperature from 50° C. to reflux,in the presence of a strong acid preferably hydrobromic acid. When theR¹ group within the definition of this process is a chlorine or fluorineatom concomitant halogen exchange may also occur to give intermediateswherein R² and R³ are as defined and R¹ represents a bromine atom.

Intermediate carboxy compounds corresponding to general formula I inwhich R¹ is as defined with the exclusion of the formyl group, R² isreplaced by the carboxy group and R³ represents an amino group may beprepared by hydrolysis of esters wherein R² is replaced by a group--COOR as defined above, preferably with an alkali metal hydroxide in asolvent such as an aqueous alcohol at a temperature from 0° C. to thereflux temperature of the reaction mixture.

Intermediate esters corresponding to general formula I in which R² isreplaced by a group --COOR as hereinbefore defined, R³ is the aminogroup, and R¹ represents a cyano or acetyl group may be prepared in asimilar manner to process version "a", described hereinbefore, fromesters ROOCCH₂ CN and intermediates of formula II wherein R⁹ representsa cyano or acetyl group.

Intermediate esters corresponding to general formula I in which R² isreplaced by a group --COOR as hereinbefore defined, R³ is the aminogroup and R¹ represents a chlorine or fluorine atom may be prepared bythe reaction of a phenylhydrazine (V) with a compound of formula XVIIIwherein X, Y and R are as hereinbefore defined, in a similar manner tothe procedure of process version "c".

Alternatively intermediates corresponding to general formula I in whichR¹ represents a chlorine or fluorine atom, R² is replaced by a hydrogenatom, and R³ represents the amino group, may be prepared by reaction ofthe corresponding aldehydes in which R² is replaced by the formyl groupwith an acid, preferably aqueous hydrochloric acid, in a solventpreferably ethanol at a temperature from . 50° C. to the refluxtemperature.

Intermediates corresponding to general formula I in which R² is replacedby a formyl group may be prepared by reaction of nitriles wherein R² isreplaced by a cyano group with a suitable reducing agent, preferablydiisobutyl aluminium hydride in an inert solvent, preferablytetrahydrofuran at a temperature from -78° C. to ambient temperature.

Intermediates corresponding to general formula I in which R² is replacedby a cyano group may be prepared by the reaction of a compound offormula XIX wherein X and Y are as hereinbefore defined (i.e.dichlorodicyanoethylene or difluorodicyanoethylene), with aphenylhydrazine (V) in a similar manner to process version "c".

Intermediates of formula XX wherein R²⁰ represents an R² group or ahydrogen atom and R³ represents a hydrogen atom or an amino group may beprepared by performing a Curtius rearrangement of the acid azidecorresponding to general formula I in which R¹ is replaced by CON₃ or inwhich R² is replaced by the hydrogen atom and R¹ is replaced by CON₃ byheating in an inert organic solvent such as toluene at a temperaturefrom 50° C. to 150° C. to give an isocyanate which is then reacted withfor example tert-butanol to give a carbamate, which-in turn ishydrolysed using dilute acid preferably hydrochloric acid in ethanol ata temperature from ambient to reflux.

Intermediate acid azides may be prepared by reaction of a carboxylicacid corresponding to general formula I in which R¹ is replaced by acarboxy group and R² and R³ are as defined above with an azide transferreagent such as diphenyl phosphoryl azide in the presence of a base,preferably triethylamine and in an inert solvent preferablyN,N-dimethylformamide, and at a temperature from 0° to 60° C.

Intermediate carboxylic acids in which R¹ is replaced by a carboxylicacid group may be prepared by hydrolysis of the corresponding esters inwhich R1 is replaced by an alkoxycarbonyl group e.g. ethoxycarbonyl,using a base such as sodium hydroxide and a solvent such as aqueousalcohol, and at a temperature from 0° C. to the reflux temperature ofthe solvent.

Intermediate carboxylic esters in which R¹ represents an alkoxycarbonylgroup and wherein R²⁰ represents R² may be prepared by reaction of anintermediate XXI wherein R and R² are as hereinbefore defined and X⁶ isa leaving group, e.g. the chlorine atom, with a phenylhydrazine V, in asimilar manner to process version "c".

Intermediate carboxylic esters in which R¹ is replaced by analkoxycarbonyl group as defined above, and R² is replaced by R²⁰, mayalternatively be prepared in a similar manner to process version "a" bythe reaction of a compound II wherein R⁹ is replaced by a --COOR groupin which R is as hereinbefore defined, with a compound of formula R²⁰CH₂ CN wherein R²⁰ is as hereinbefore defined.

Intermediates corresponding to formula II in which R⁹ is replaced by--COOR may be prepared from known compounds (e.g. CH₃ COCH(Cl)COOR) in asimilar manner to that described above for compounds of formula IIwherein R⁹ represents a cyano or acetyl group.

Intermediate halides of formula XXI wherein X⁶ represents a chlorineatom and R and R² are as hereinbefore defined, may be prepared by thereaction of the sodium or potassium salts XXI wherein X⁶ is --O⁻ Na⁺ or--O⁻ K⁺ with a suitable chlorinating agent, preferably phosphorusoxychloride, optionally in the presence of an inert solvent, e.g.tetrahydrofuran, and at a temperature from 0° C. to the refluxtemperature of the solvent.

Intermediate salts XXI wherein X⁶ is --O⁻ Na⁺ or --O⁻ K⁺ may be preparedby methods described in the literature, wherein active methylenecompounds R² CH₂ CN are reacted with dialkyl oxalates, e.g. diethyloxalate, in the presence of a metal alkoxide, e.g. sodium ethoxide, inan inert solvent, e.g. an alcohol such as ethanol, and at a temperaturefrom 25° C. to the reflux temperature of the solvent.

Intermediates corresponding to general formula I in which R¹ is replacedby a 1-hydroxyethyl group may be prepared by the reaction of aldehydesof general formula I wherein R¹ represents a formyl group and R³represents the hydrogen atom or an amino group with a Grignard reagent,preferably methyl magnesium halide, in an inert solvent, e.g. ether ortetrahydrofuran, and at a temperature from ambient to the refluxtemperature of the solvent.

Intermediate 4-thiocyanatopyrazoles corresponding to general formula Iin which R² is replaced by the thiocyanato group and R³ represents theamino group may be prepared by the reaction of a compound correspondingto general formula I in which R² is replaced by the hydrogen atom with athiocyanating agent, such as alkali metal or ammonium salts ofthiocyanic acid (e.g. NaSCN) and bromine, in an inert organic solvent,such as methanol, and at a temperature from 0° C. to 100° C.

Intermediate disulphides of formula VIII may be prepared by thehydrolysis of thiocyanates in which R² is replaced by the thiocyanatogroup and R¹ represents a chlorine, bromine or fluorine atom or thecyano or nitro group using hydrochloric acid in the presence of ethanolor by reduction with sodium borohydride in ethanol, both being at atemperature from ambient to reflux. Alternatively the thiocyanates maybe converted into compounds of formula VIII by treatment with base,preferably aqueous sodium hydroxide and preferably under phase-transferconditions with chloroform as co-solvent and in the presence of a phasetransfer catalyst e.g. triethylbenzylammonium chloride and at atemperature from ambient to 60° C.

Intermediate diaminoesters corresponding to general formula I in whichR¹ and R³ represent the amino group and R² is replaced by an ester group--COOR as hereinbefore defined containing from 2 to 7 carbon atoms, maybe prepared by reaction of an appropriately substituted phenylhydrazineof formula V with an alkali metal salt of an alkyl dicyanoacetate offormula XXII:

    ROOC--CH(CN).sub.2                                         (XXII)

(wherein R is as hereinbefore defined) preferably potassium ethyldicyanoacetate using hydrochloric acid, at ambient to refluxtemperature. Alkyl dicyanoacetate potassium salts may be prepared byreaction of the appropriate alkyl chloroformate with malononitrile inthe presence of potassium hydroxide in tetrahydrofuran at a temperatureof 0° to 100° C.

Intermediate diaminosulphonylpyrazoles corresponding to general formulaI in which R¹ and R³ represent the amino group and R² represents asulphonyl group R'SO₂ may be prepared in a similar manner to the processjust described by reaction of a phenylhydrazine (V) with an alkali metalsalt of a suitable alkylsulphonylmalononitrile of formula XXIII:

    R'SO.sub.2 --CH(CN).sub.2                                  (XXIII)

(wherein R is as hereinbefore defined).

The preparation of compounds of formula XXIII is described in theliterature.

Intermediate esters corresponding to general formula I in which R¹represents a chlorine, bromine or fluorine atom or a nitro group, R² isreplaced by a group --COOR as hereinbefore defined, and R³ is an aminogroup, may be prepared in a similar manner to process version "f" viadiazotisation of compounds corresponding to general formula I in whichR¹ is replaced by an amino group.

Intermediate esters corresponding to general formula I in which R¹ isreplaced by a group --COOR as hereinbefore defined, R² is replaced bythe hydrogen atom, and R³ represents an amino group, may also beprepared from the reaction of a phenylhydrazine of formula V with analkali metal salt of formula XXIV wherein M is sodium or potassium and Ris as hereinbefore defined. The reaction is performed in an acidicmedium generally dilute sulphuric acid, optionally in the presence of aco-solvent e.g. ethanol, and at a temperature from ambient to the refluxtemperature of the solvent.

According to a further feature of the present invention there areprovided intermediates of formula XXV, useful in the preparation ofcompounds of general formula I, wherein R² ' is as defined for R² orrepresents the hydrogen atom, a thiocyanato, formyl, cyano or carboxygroup, a straight- or branched-chain alkoxycarbonyl group containingfrom 2 to 7 carbon atoms or the dithio group (which joins two pyrazolerings for example as in formula VIII), R³ ' is as defined for R³ orrepresents the diphenoxycarbonylamino group, and R¹ ' is as defined forR¹ or represents the amino, 1-hydroxyethyl, carboxy or carbamoyl groupor a straight- or branched-chain alkoxycarbonyl or alkoxycarbonylaminogroup containing from 2 to 7 carbon atoms, with the exclusion ofcompounds of general formula I and of those compounds of formula XXVwherein R⁴ and R⁸ are chloro and R⁶ is trifluoromethyl, i.e.,2,6-dichloro-4-trifluoromethylphenyl, R² ' represents the cyano group,R¹ ' represents the cyano group and R³ ' represents the amino,acetamido, dichloroacetamido, t-butylcarbonylamino, propionamido,pentanamido, bis(ethoxycarbonyl)amino, ethoxycarbonylamino, methylaminoor ethylamino group,

or R¹ ' represents the chlorine atom and R³ ' represents the amino,t-butylcarbonylamino, bis(ethoxycarbonyl)amino or ethoxycarbonylaminogroup,

or R¹ ' represents a bromine or iodine atom or an amino orethoxycarbonyl group and R³ ' represents the amino group,

or R¹ ' represents the fluorine atom and R³ ' represents the hydrogenatom or the amino group,

or R¹ ' represents a nitro, amino, t-butoxycarbonylamino orethoxycarbonyl group and R³ ' represents the hydrogen atom;

the phenyl group with substituents R⁴ -R⁸ represents a2,4,6-trichlorophenyl, 2-chloro-4-trifluoromethylphenyl or2,6-dichloro-4-trifluoromethoxyphenyl group, R² ' represents the cyanogroup, R¹ ' represents the cyano group and R³ ' represents the aminogroup;

the phenyl group with substituents R⁴ -R⁸ represents a2,6-dichloro-4-trifluoromethoxy group, R² ' represents the cyano group,R¹ ' represents the chlorine atom and R³ ' represents the amino group;and the phenyl group is the 2,6-dichloro-4-trifluoromethylphenyl group,R² ' represents the methanesulphonyl group, R¹ ' represents a carboxy,carbamoyl or ethoxycarbonyl group and R³ ' represents the amino group.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole is apreferred intermediate.

The following Examples and Reference Examples illustrate the preparationof compounds of general formula I according to the present invention:

[Chromatography was effected on a silica column (May & Baker Ltd 40/60flash silica) at a pressure of 6.8 Nm⁻², unless otherwise stated.]

EXAMPLE 1 Compounds Nos. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 90

A solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole (20.0g) in dichloromethane (100 ml) was stirred magnetically and treateddropwise with a solution of trifluoromethylsulphenyl chloride (10.8 g)in dichloromethane (50 ml) during 1 hour. The solution was stirredovernight at room temperature, then washed with water (100 ml), driedover anhydrous magnesium sulphate, filtered, and evaporated in vacuo togive a solid (26.3 g). This solid was recrystallised from toluene/hexaneto give5-amino-3-cyano-1-(2,6-dichloro4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazoleas fawn crystals (24.2 g) m.p. 169°-171° C. By proceeding in a similarmanner but replacing the5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole by thehereinafter indicated appropriately substituted pyrazole there wasobtained from trifluoromethyl-sulphenyl chloride unless otherwisestated:

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-trifluoro-methylthiopyrazole,m.p. 125°-126° C., in the form of pale yellow crystals, from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-pyrazole.

5-Amino-3-cyano-1-(2,6-dichloro-4-difluoromethoxyphenyl)-4-trifluoromethylthiopyrazole,m.p. 127°-128.5° C., in the form of a buff solid, from5-amino-3-cyano-1-(2,6-dichloro-4-difluoromethoxyphenyl)pyrazole.

5-Amino-1-(2-chloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole,m.p. 142°-144° C., in the form of a light brown solid, from5-amino-1-(2-chloro-4-trifluoromethylphenyl)-3-cyanopyrazole.

5-Amino-3-cyano-1-(2,4,6-trichlorophenyl)-4-trifluoromethylthiopyrazole,m.p. 192°-193° C., in the form of brown crystals, from5-amino-3-cyano-1-(2,4,6-trichlorophenyl)pyrazole.

5-Amino-3-cyano-1-(2,6-dibromo-4-trifluoromethylphenyl-4-trifluoromethylthiopyrazole,m.p. 202°-204° C., in the form of orange crystals, from5-amino-3-cyano-1-(2,6-dibromo-4-trifluoromethylphenyl ) pyrazole.

5-Amino-1-(2-bromo-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole,m.p. 136°-138° C., in the form of a pale yellow solid, from5-amino-1-(2-bromo-4-trifluoromethylphenyl)-3-cyanopyrazole.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-difluoromethylthiopyrazole,m.p. 159°-161° C., in the form of a light brown solid, from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole anddifluoromethylsulphenyl chloride.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-heptafluoropropylthiopyrazole,m.p. 148°-150° C., in the form of a yellow solid, after dry column flashchromatography on silica eluting with dichloromethane and petroleumether (2:1), from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole andheptafluoropropylsulphenyl chloride.

5-Amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole,m.p. 183°-185° C., in the form of yellow crystals, from5-amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-3-cyanopyrazole andemploying tetrahydrofuran as solvent.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trichloromethylthiopyrazole,m.p. 245°-247° C., in the form of a white solid after purification bychromatography, starting from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole andtrichloromethylsulphenyl chloride.

By proceeding in a similar manner but replacing thetrifluoromethylsulphenyl chloride by dichlorofluoromethylsulphenylchloride, and by the addition of a molar equivalent of pyridine to thereaction mixture after stirring overnight there was obtained:

5-Amino-3-cyano-4-dichlorofluoromethylthio-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole,m.p. 178°-180° C. in the form of a white solid, after purification bychromatography eluting with diethyl ether/hexane (1:1), from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

By proceeding in a similar manner but employing a molar equivalent ofpyridine in the reaction solution there was obtained:

5-Amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.m.p. 149°-150.5° C., in the form of a white solid, afterrecrystallisation from hexane from5-amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole,m.p. 154.5°-156° C., in the form of a white solid, afterrecrystallisation from hexane/ethyl acetate and then fromhexane/cyclohexane, starting from5-amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-fluoro-4-trifluoromethylthiopyrazole,m.p. 123°-126° C., in the form of a white solid, starting from5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-fluoropyrazole.

5-Amino-4-chlorodifluoromethylthio-3-cyanol-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole,m.p. 167°-168° C., in the form of a white solid, starting fromchlorodifluoromethylsulphenyl chloride. The product was purified by highperformance liquid chromatography employing a 8 micron irregular column(21.4 mm×25 cm) and eluting with acetonitrile/water (3:2).

Reference Example 1

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole used inthe above Example was prepared as follows:

A suspension of nitrosyl sulphuric acid prepared from sodium nitrite(7.0 g) and concentrated sulphuric acid (27.5 ml) was diluted withacetic acid (25 ml), cooled to 25° C., and stirred mechanically. To thiswas added a solution of 2,6-dichloro-4-trifluoromethylaniline (21.2 g)in acetic acid (50 ml) dropwise over 15 minutes at 25°-32° C. Thismixture was heated to 55° C. for 20 minutes and poured onto a stirredsolution of ethyl 2,3-dicyanopropionate (14.0 g) in acetic acid (60 ml)and water (125 ml) at 10°-20° C. After 15 minutes, water (200 ml) wasadded, and the oily layer separated. The aqueous solution was thenextracted with dichloromethane (3×70 ml) and the extracts combined withthe oil and washed with ammonia solution (to pH9). The organic phase wasthen stirred with ammonia (20 ml) for 2 hours, and the dichloromethanelayer then separated. This was washed with water (1×100 ml), 1Nhydrochloric acid (1×100 ml), dried over anhydrous magnesium sulphate,filtered, and evaporated in vacuo to give an oily solid. Crystallisationfrom toluene/hexane gave the title compound as brown crystals (20.9 g),m.p. 140°-142° C.

By proceeding in a similar manner but replacing the2,6-dichloro-4-trifluoromethylaniline by the appropriately substitutedanilines there was obtained:5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl) pyrazole inthe form of a fawn solid, m.p. 119°-120.5° C., from2,6-dichloro-4-trifluoromethoxyaniline.

5-Amino-3-cyano-1-(2,6-dichloro-4-difluoromethoxyphenyl)pyrazole, afterwashing the initially formed product as a solution in dichloromethanewith saturated sodium carbonate solution. The title compound wasobtained as a yellow solid after recrystallisation from toluene, m.p.120.5°-122.5° C., from 2,6-dichloro-4-difluoromethoxyaniline.

5-Amino-1-(2-chloro-4-trifluoromethylphenyl)-3-cyanopyrazole in the formof an orange crystalline solid, m.p. 133°-135° C., from2-chloro-4-trifluoromethylaniline-5-Amino-3-cyano-1-(2,4,6-trichlorophenyl)pyrazolein the form of a light brown solid, m.p. 155°-156° C., from2,4,6-trichloroaniline.

5-Amino-3-cyano-1-(2,6-dibromo-4-trifluoromethylphenyl)pyrazole in theform of a yellow crystalline solid, m.p. 142°-146° C., from2,6-dibromo-4-trifluoromethylaniline.5-Amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-3-cyanopyrazole inthe form of a brown crystalline solid, m.p. 146°-148° C., from2-bromo-6-chloro-4-trifluoromethylaniline

5-Amino-1-(2-bromo-4-trifluoromethylphenyl)-3-cyanopyrazole in the formof a yellow crystalline solid, m.p. 159°-162° C., from2-bromo-4-trifluoromethylaniline.

5-Amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole, usedin Example 1, was prepared as follows:

A mixture of5-amino-3-chloro-1-(2,6-dichloro-4trifluoromethylphenyl)-4-ethoxycarbonylpyrazole(5.0 g) and hydrochloric acid (6N; 75 ml) in glacial acetic acid (75 ml)was heated at reflux for 24 hours. The cooled reaction mixture wasevaporated to low bulk and basified to pH 12 with sodium hydroxide (2N)and extracted with dietnyl ether (3×75 ml). The ether extracts werecombined and evaporated in vacuo to give a mixture of 5-amino and5-acetamido pyrazoles in the form of a yellow gummy solid (3.5 g). Thissolid was dissolved in a mixture of hydrochloric acid (6N; 30 ml) anddioxan (60 ml) and heated at reflux for 48 hours. The volatiles wereremoved in vacuo and the residue purified by column chromatography usingdichloromethanehexane (4:1). Evaporation of the eluate containing themajor component gave the title compound (1.3 g), m.p. 128°-129° C., inthe form of an off-white solid.

5-Amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethoxycarbonylpyrazole,used above, was prepared as follows:

Tertiary-butyl nitrite (15.0 g) was added dropwise to a stirred andcooled (0° C.) mixture of3,5-diamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethoxycarbonyl-pyrazole(50.0 g) and cupric chloride (21.0 g) in acetonitrile (600 ml) over 10minutes. The reaction mixture was stirred for 2 hours at 0° C. and 2hours at laboratory temperature then evaporated to low bulk and pouredinto hydrochloric acid (5N; 1500 ml). The resultant solution wasextracted with dichloromethane (3×600 ml), washed with hydrochloric acid(2N; 2×600 ml), dried over anhydrous magnesium sulphate and evaporatedto furnish a brown tar. The tarry material was removed from the productusing a dry silica chromatography eluted with dichloromethane-hexane(4:1), further purification by column chromatography using hexanecontaining increasing proportions of dichloromethane (60 to 80%) gavethe title compound (15.8 g), m.p. 143°-146.5° C., in the form of anorange solid.

3,5-Diamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethoxycarbonylpyrazole,used above, was prepared as follows:

Ethyl dicyanoacetate potassium salt (35.2 g) was added to a stirredsuspension of 2,6-dichloro-4-trifluoromethylphenylhydrazine (49 g) inhydrochloric acid (0.9N; 220 ml) and the reaction mixture stirred andheated at reflux for 18 hours. The reaction mixture was then cooled toprecipitate a solid which was filtered off, triturated with diethylether (250 ml) and dried to give an off-white solid (56 g) which wasrecrystallised from a mixture of ethyl acetate and hexane to give thetitle compound (29.2 g), m.p. 196°-197° C., in the form of an off-whitesolid.

Ethyl dicyanoacetate potassium salt was prepared as follows:

A solution of ethyl chloroformate (520 g) and malononitrile (330 g) intetrahydrofuran (500 ml) was added dropwise over one hour to a stirredsolution of potassium hydroxide (560 g) and water (2.01) at atemperature below 40° C. (external ice cooling). The reaction mixturewas stirred at laboratory temperature for 1 hour then cooled to 0° C. toprecipitate a solid which was filtered off and dried over phosphoruspentoxide to give the title compound, (334.4 g) in the form of anoff-white solid.

5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole, usedin the above Example, was prepared as follows:

A mixture of5-amino-4-carbethoxy-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole(3.3 g) and hydrobromic acid (48%, 30 ml) in glacial acetic acid (50 ml)was heated at reflux for 18 hours. The mixture was evaporated to lowbulk, basified with sodium hydroxide solution (1N) and the productfiltered off and dried (2.9 g). Recrystallisation from a mixture ofethanol and water gave the title compound (2.5 g), m.p. 132.5°-134° C.,in the form of a colourless solid.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-fluoropyrazole, usedin the above Example was prepared as follows:

A mixture of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-fluoro-4-formylpyrazole(1.5 g) in methanol (40 ml) and 2N hydrochloric acid (10 ml) was heatedunder reflux for 24 hours. After evaporation in vacuo, water (100 ml)was added, and the mixture extracted with ethyl acetate (2×100 ml). Theextract was washed with saturated sodium bicarbonate solution (50 ml),dried over anhydrous magnesium sulphate, and evaporated in vacuo.Purification by chromatography eluting with dichloromethane gave thetitle compound, m.p. 128°-129° C., in the form of a white solid.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-fluoro-4-formylpyrazole,used above, was prepared as follows:

A stirred solution of5-amino-4-cyano-(2,6-dichloro-4-trifluoromethylphenyl)-3-fluoropyrazole(preparation described in PCT Patent Publication WO 8703-781-A) (2.2 g)in dry tetrahydrofuran (40 ml) was treated at -70° C. under nitrogenwith a solution of diisobutylaluminium hydride (13 ml of a 1M toluenesolution). The mixture was allowed to warm to room temperature over 2hours, left overnight, and poured onto a mixture of 2N hydrochloric acid(50 ml) and ice (50 g). After stirring for 1/2 hour, toluene (25 ml) wasadded, and the organic layer separated. The aqueous layer wasre-extracted with dichloromethane (2×100 ml), and the combined organicsolution washed with sodium bicarbonate solution (20 ml) and dried overanhydrous magnesium sulphate. Evaporation in vacuo gave a brown solid(1.5 g), which was purified by chromatography eluting with toluene/ethylacetate (98:2) to give the title compound (1.0 g), m.p. 137°-139.5° C.,in the form of a pale yellow solid.

EXAMPLE 2 Compounds Nos. 16, 17

A mixture of anhydrous cupric chloride (1.15 g) in acetonitrile (20 ml)was stirred whilst tert-butyl nitrite (0.73 g) was added at 0° C. After10 minutes, a solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(3.0 g) in acetonitrile (5 ml) was added at 0° C. and the mixturestirred at 0° C. for 2 hours, and then at room temperature overnight.After evaporation in vacuo the residue was dissolved in a mixture ofdichloromethane (50 ml) and hydrochloric acid (5M; 50 ml). The organiclayer was dried over anhydrous magnesium sulphate, evaporated in vacuoand then purified by chromatography, eluting with petroleum ether (b.p.60°-80° C.)/dichloromethane (2:1). Recrystallisation of the resultantproduct from petroleum ether (b.p. 60°-80° C.) gave5-chloro-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(0.55 g) as a white crystalline solid, m.p. 131°-132° C. By proceedingin a similar manner but starting from3,5-diamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazoleand performing the reaction at 0° C. for 2 hours and then warming toreflux temperature there was obtained:

5-Amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole,m.p. 177°-179° C., in the form of a white solid, after purification bychromatography eluting with dichloromethane, and then recrystallisingfrom toluene/hexane.

Reference Example 2

3,5-Diamino-1-(2,6-dichloro-4-trifluoromethylphenyl)4-methanesulphonylpyrazole, used in the above Example, was prepared asfollows:

Potassium carbonate (11.7 g) was added portionwise to a stirred mixtureof methanesulphonylmalononitrile hydrochloride (30.0 g) in water (150ml). 2,6-Dichloro-4-trifluoromethylphenylhydrazine (41.0 g) was thenadded and the mixture heated at 100° C. overnight. After cooling theyellow solid was filtered, washed with water, and recrystallised fromaqueous methanol. This solid was washed thoroughly with ether, yieldingthe title compound as a white solid (14.6 g) m.p. 224°-226° C.

EXAMPLE 3 Compounds Nos. 18, 19, 20, 99

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(4.0 g) was added to triethyl orthoformate (19.0 ml) andp-toluene/-sulphonic acid (0.019 g) added. The mixture was heated underreflux for 21 hours, cooled, and the triethyl orthoformate evaporated invacuo to give a brown oil as residue. This was purified bychromatography eluting with a mixture of dichloromethane and hexane(1:1). Evaporation of the eluates in vacuo gave3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxymethyleneamino-4-trifluoromethylthiopyrazoleas a colourless solid, m.p. 70°-71.5° C.

By proceeding in a similar manner but replacing the triethylorthoformate with triethyl orthoacetate and employing toluene asco-solvent there was obtained:3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)5-ethoxyethylideneamino-4-trifluoromethylthiopyrazole as a pale yellowsolid, m.p. 71°-73° C.

By proceeding in a similar manner but replacing the5'amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4trifluoromethylthiopyrazoleby5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole,and by employing triethyl orthoformate and toluene, there was obtained:

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)5-ethoxymethyleneamino-4-methanesulphonylpyrazole,m.p. 145°-147° C., in the form of a cream solid.

By proceeding in a similar manner there was prepared from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphonylpyrazoleand triethyl orthoformate and in the absence of toluene as co-solvent,3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxymethyleneamino-4-trifluoromethylsulphonylpyrazole,m.p. 118.8°-119.8° C., in the form of a white solid, and afterrecrystallisation from hexane.

EXAMPLE 4 Compounds Nos. 21, 22, 23, 24, 96

To a stirred solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(4.0 g) and acetyl chloride (2.3 g) in acetonitrile (40 ml) at 0° C. wasadded pyridine (1.3 ml) dropwise. The yellow solution was warmed to roomtemperature during 45 minutes and then heated under reflux for 24 hours.The cooled solution was evaporated in vacuo and the residue dissolved indichloromethane (100 ml), washed with water (2×100 ml), dried overanhydrous magnesium sulphate and evaporated in vacuo to give a buffsolid (4.2 g). This was purified by chromatography eluting withdichloromethane to give5-acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethyl-thiopyrazole(2.0 g) as a colourless solid, m.p. 217°-218° C., afterrecrystallisation from toluene.

By proceeding in a similar manner but replacing the acetyl chloride bypropionyl chloride there was obtained the following two compounds:

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis (propionyl)amino-4 -trifluoromethylthiopyrazole, m.p. 128°-130° C., in the form ofa white crystalline solid, and 3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-propionamido-4-trifluoromethylthiopyrazole, m.p. 178.5°-182° C., inthe form of a pale yellow solid. By proceeding in a similar manner, butreplacing the5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazoleby5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole,there was obtained:

5-Acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole,m.p. 220°-222° C., in the form of a cream solid.

By proceeding in a similar manner there was obtained5-acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethysulphinylpyrazole,m.p. 208°-211° C., in the form of a white solid, from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl-4-trifiuoromethylsulphinylpyrazole.The reaction mixture was heated at reflux for 3 hours in this instance.

EXAMPLE 5 Compounds Nos. 25, 26, 27, 28, 29, 30, 97

To a stirred solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(5.0 g) in dry tetrahydrofuran (80 ml) stirred under nitrogen at roomtemperature, was added sodium hydride (0.36 g of an 80% oil dispersion)during 1/2 hour. After a further 1/2 hour, 2 drops of 151crown-5followed by trimethylacetyl chloride (1.6 g) was added, and the mixtureheated under reflux for 24 hours. After cooling to 0° C. a furtheraddition of sodium hydride (0.15 g) followed by trimethylacetyl chloride(0.8 g) was made, and the mixture refluxed for another 18 hours. Themixture was cooled, poured onto water (100 ml) and extracted with ether(2×80 ml). The ether extracts were dried over anhydrous magnesiumsulphate, and evaporated in vacuo to give a yellow oil (6.2 g), whichwas purified by chromatography eluting with petroleumether/dichloromethane (3:2) to give3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthio-5-trimethylacetamidopyrazole(0.82 g), m.p. 172.5°-173.5° C., in the form of a white solid.

By proceeding in a similar manner but replacing the trimethylacetylchloride by the appropriate acylating agents there was prepared:

3-Cyano-1-(2.6-dichloro-4-trifluoromethylphenyl)-5-bis(methoxycarbonyl)amino-4-trifluoromethylthiopyrazole,m.p. 135°-136.5° C., in the form of a white solid, using methylchloroformate.

3-Cyano-1-(2.6-dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-4-trifluoromethylthiopyrazole,m.p. 83.2°-85.5° C., in the form of a white solid, using ethylchloroformate and performing the reaction at ambient temperature.

5-Chloroacetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole,m.p. 175°-176° C., in the form of a white solid, using chloroacetylchloride, and after purification by chromatography and recrystallisationfrom toluene/hexane.

By proceeding in a similar manner but replacing the5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl-4-trifluoromethylthiopyrazoleby5-amino-3-cyrano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazoleand by the use of appropriate acylating agents, there was prepared:

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-4-methanesulphonylpyrazolein the form of a white solid, m.p. 195°-198° C., using ethylchloroformate.

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-5-trimethylacetamidopyrazolein the form of a white solid, m.p. 245°-247° C., using trimethylacetylchloride.

By proceeding in a similar manner there was prepared from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphonylpyrazoleand ethyl chloroformate:

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-4-trifluoromethylsulphonylpyrazole,m.p. 116°-116.9° C., in the form of a white solid, afterrecrystallisation from toluene/hexane.

EXAMPLE 6 Compounds Nos. 31, 32, 33, 34, 35, 36, 93

To a mixture of sodium hydride (0.71 g of an 80% oil dispersion) in drytetrahydrofuran (30 ml) was added5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(4.0 g). After 20 minutes, 3 drops of 15-crown-5 was added and themixture cooled to 0° C. Methyl iodide (3.4 g) was then added and themixture stirred at 0° C. for 1/2 hour, then at room temperatureovernight. The solvent was evaporated in vacuo and the residuepartitioned between dichloromethane (80 ml) and water (80 ml). Theorganic phase was dried over anhydrous magnesium sulphate, andevaporated in vacuo to give a pale yellow solid (4.29 g). Purificationby chromatography eluting with dichloromethane/petroleum ether (1:1)gave3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dimethylamino-4-trifluoromethylthiopyrazole(2.11 g), m.p. 109.5°-110.8° C., in the form of a white solid.

By proceeding in a similar manner but replacing the methyl iodide by theappropriate alkyl halides there was prepared:

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-isopropylamino-4-trifluoromethylthiopyrazole,m.p. 173°-175° C., in the form of a cream solid after purification bychromatography and recrystallisation from toluene/hexane, prepared fromisopropyl iodide.3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-propylamino-4-trifluoromethylthiopyrazole,m.p. 162°-163.5° C., in the form of a white solid, and:

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dipropylamino-4-trifluoromethylthiopyrazole,m.p. 72.5°-73° C., in the form of a white solid, both compounds preparedusing propyl bromide and performing the reaction initially at 0° C. andthen at 70° C.

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(propargyl)amino-4-trifluoromethylthiopyrazole,m.p. 86°-89° C., in the form of a white solid after recrystallisationfrom toluene/hexane, prepared from propargyl bromide.

By proceeding in a similar manner but replacing the5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazoleby5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole,and using methyl iodide as alkylating agent, there was prepared:

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methylamino-4-methanesulphonylpyrazolein the form of a yellow solid, m.p. 169°-172° C.

By proceeding in a similar manner but replacing the5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluromethylthiopyrazoleby5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphinylpyrazoleand employing dioxan as solvent and heating under reflux for 5 hours wasobtained3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dimethylamino-4-trifluoromethylsuphinylpyrazole,m.p. 154°-161° C., in the form of a white solid.

EXAMPLE 7 Compounds Nos. 37, 38, 39, 40, 41, 95

A suspension of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethanesulphonylpyrazole(43.8 g) was stirred in a mixture of bromoform (141 ml) and dryacetonitrile (63 ml). Tert-butyl nitrite (29.9 g) was added dropwiseduring 5 minutes, and the mixture heated at 60°-70° C. for 2.75 hours.After cooling to 25° C. a further addition of tert-butyl nitrite (29.9g) was made, and the heating resumed for 2 hours. Evaporation in vacuogave a yellow oily solid which was triturated with hexane and filteredoff. Two recrystallisations from toluene/hexane gave5-bromo-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)4-trifluoromethanesulphonylpyrazoleas a yellow solid (34.0 g), m.p. 136°-137° C.

By proceeding in a similar manner but replacing the5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethanesulphonylpyrazoleby the following phenylpyrazoles there was obtained:

5-Bromo-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole,m.p. 161.5°-164° C., in the form of a buff solid, from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.Acetonitrile was not employed as co-solvent for this preparation.

5-Bromo-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole,m.p. 160.5°-162° C., in the form of a white solid, from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole.

5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole,m.p. 193°-195° C., in the form of a white solid, from3,5-diaminol-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole(preparation described in Reference Example 2), and by replacing thebromoform by two equivalents of bromine and by employing chloroform assolvent.

3-Bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)4-methanesulphonylpyrazolein the form of white crystals, m.p. 178°-180° C. from3-amino-1-(2,6-dichloro4-trifluoromethylphenyl)-4-methanesulphonylpyrazole.By proceeding in a similar manner there was obtained:

5-Bromo-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphinylpyrazole,m.p. 147°-48° C., in the form of a yellow solid. The reaction wasperformed at 52° C. for 2 hours in this instance.

Reference Example 3

3-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazoleused in the Example above was prepared as follows:

A solution of3-tert-butoxycarbonylamino-1-(2,6-dichloro-4-trifluoromethylphenyl)4-methanesulphonylpyrazole(6.4 g) in ethanol (150 ml) was treated with 50% v/v hydrochloric acid(20 ml), and the mixture refluxed for 1 hour. The solvent was evaporatedin vacuo and the residue dissolved in dichloromethane, washed withsodium bicarbonate solution, then with water, dried over anhydrousmagnesium sulphate and evaporated in vacuo. The product wasrecrystallised from ethyl acetate/hexane to give the title compound (3.0g) as white crystals, m.p. 222°-223° C.

3-tert-Butoxycarbonylamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazolewas prepared as follows:

A mixture of3-carboxy-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole(9.4 g), and thionyl chloride (70 ml) and N,N-dimethylformamide (3drops) was heated under reflux for 2 hours. The solvent was evaporatedin vacuo and re-evaporated in vacuo after addition of dry toluene (20ml). The resultant solid was dissolved in dry acetone (60 ml) andstirred, whilst a solution of sodium azide (2.1 g) in water (15 ml) wasadded during 5 minutes keeping at 10°-15° C. After 30 minutes themixture was poured onto water (250 ml) and extracted withdichloromethane (3×80 ml). The combined extract was washed with water,dried over anhydrous magnesium sulphate, and evaporated in vacuo atequal to or below 40° C. to give a fawn solid.

The resulting azide was dissolved in dry toluene (80 ml) and heatedunder reflux for 0.75 hour, with smooth evolution of nitrogen. Aftercooling, this was treated with tert-butanol (15 g), and the mixtureheated under reflux for two hours. After standing overnight at roomtemperature and evaporation in vacuo, the resulting brown semi solid(9.2 g) was purified by chromatography on silica (Merck 230-400 mesh,6.8 Nm⁻²) eluting with dichloromethane and ethyl acetate (98:2) to givethe title compound (6.6 g).

3-Carboxy-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazolewas prepared as follows:

A mixture of1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-methanesulphonylpyrazole(14.0 g) and 80% sulphuric acid (300 ml) was heated and stirred at 80°C. for 4 hours. After standing at room temperature overnight, thesolution was poured onto excess ice and the precipitated solid filteredoff. This was dissolved in ethyl acetate, washed with water, dried(anhydrous magnesium sulphate) and evaporated to give the title compoundas a buff solid (11.1 g), m.p. 215°-216° C.

1-(2,6-Dichloro-4-trifluoromethylphenyl)3-ethoxycarbonyl-4-methanesulphonylpyrazole,used above, was prepared as follows:

To a solution of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-methanesulphonylpyrazole(17.1 g) in dry tetrahydrofuran (130 ml) stirred at room temperature,was added during 2 minutes, tert-butyl nitrite (33 ml). The mixture washeated at reflux for 1.5 hours, the solvent evaporated in vacuo, and theresidue dissolved in dichloromethane. After washing with water, drying(anhydrous magnesium sulphate), and evaporation a yellow solid wasobtained. Recrystallisation from toluene-petroleum ether (b.p. 60°-80°C.) gave the title compound as yellow crystals (15.2 g), m.p. 183°-185°C.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-methanesulphonylpyrazole,used above, was prepared as follows:

To absolute ethanol (20 ml) cooled in an ice-water bath was added sodiumhydride (0.25 g of an 80% oil dispersion), followed bymethanesulphonylacetonitrile (0.99 g) and the mixture stirred for 1/2hour. A solution of ethylchloro(2,6-dichloro-4-trifluoromethylphenyl)hydrazonoacetate (3.0 g) inabsolute ethanol (20 ml) was then added, and stirring continued for 5hours. The yellow solid was filtered off (2.55 g) and recrystallisedfrom ethanol to give the title compound as a colourless solid, m.p. 255°C. Ethyl chloro(2,6-dichloro-4-trifluoromethylphenyl)hydrazonoacetatewas prepared as follows:

Sodium nitrite (3.04 g) was added during 15 minutes to stirredconcentrated sulphuric acid (24 ml) at 30°-50° C. The solution wascooled to 20° C., and added dropwise during 15 minutes to a solution of2,6-dichloro-4-trifluoromethylaniline (9.2 g) in acetic acid (90 ml),maintaining at 35°-40° C. This solution was then cooled to +10°, andadded dropwise to a stirred solution of anhydrous sodium acetate (54 g)and ethyl chloroacetoacetate (7.0 g) in a mixture of water (72 ml) andethanol (48 ml) during 45 minutes with cooling such that the temperaturewas kept at 10° C. After 1 hour at room temperature the mixture wasdiluted with water, filtered, and the solid dissolved indichloromethane. This solution was dried over anhydrous magnesiumsulphate, filtered, and evaporated in vacuo to give the title compoundas a white solid (11.9 g), m.p. 96°-98° C.

EXAMPLE 8 Compounds Nos. 42, 43, 44, 45

A solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(4.0 g) in dry tetrahydrofuran (20 ml) was treated with tert-butylnitrite (5.76 g) at room temperature. The mixture was then heated underreflux for 3 hours and evaporated in vacuo to give a yellow solid.Purification by chromatography eluting with petroleumether/dichloromethane (2:1) gave3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)4-trifluoromethylthiopyrazole(3.12 g), m.p. 126.5°-128° C., in the form of a white solid. Byproceeding in a similar manner but replacing the5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazoleby the following phenylpyrazoles, there was obtained:

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)4-trifluoromethanesulphonylpyrazole,m.p. 149°-151° C., in the form of a white solid, from5-amino-3-cyano-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethanesulphonylpyrazole.The product was obtained after 29 hours heating under reflux, followedby purification by chromatography and recrystallisation fromtoluene/hexane.

3-Cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)4-trifluoromethylthiopyrazole,m.p. 64°-65° C., in the form of a white solid, from5-amino-3-cyano-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-trifluoromethylthiopyrazole.

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)4-methanesulphonylpyrazole,m.p. 147°-150° C., in the form of yellow crystals, from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole.

EXAMPLE 9 Compounds Nos. 46, 47, 48, 49, 50, 94

To a solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(3.0 g) in chloroform (50 ml) stirred at room temperature, was addediodine (3.61 g). Tert-butyl nitrite (1.43 g) was then added and after1/2 hour the mixture was heated under reflux for 2 hours, then left atroom temperature overnight. The solid was filtered off, washed withdichloromethane (50 ml) and the combined filtrate washed with sodiumthiosulphate solution (2×50 ml) and then with water (50 ml). Afterdrying over anhydrous magnesium sulphate, the solution was evaporated invacuo to give a yellow solid (3.8 g), which was purified bychromatography eluting with petroleum ether/dichloromethane (2:1).Recrystallisation from toluene/hexane gave3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-iodo-4-trifluoromethylthiopyrazole,m.p. 187.3°-188.3° C., in the form of a white solid.

By proceeding in a similar manner but replacing the5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazoleby the following phenylpyrazoles, there was obtained:

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-iodo-4-trifluoromethylsulphonylpyrazole,m.p. 180°-181° C., in the form of a white solid; from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethanesulphonylpyrazole.In this instance the reaction mixture was heated under reflux for 24hours.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-iodo-4-methanesulphonylpyrazole,m.p. 226°-227° C., in the form of a brown solid; from3,5-diamino-1-(2,6-dichloro-4-trifluoromethylphenyl)4-methanesulphonylpyrazole.The reaction mixture was heated under reflux for 41/2 hours in thiscase.1-(2,6-Dichloro-4-trifluoromethylphenyl)-3-iodo-4-methanesulphonylpyrazole,in the form of a cream solid, m.p. 150°-151° C., prepared from3-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole(preparation described in Reference Example 3).1-(2,6-Dichloro-4-trifluoromethylphenyl)-3-iodo-4-trifluoromethylthiopyrazole,m.p. 80°-81.5° C., in the form of a white solid, prepared from3-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)4-trifluoromethyl-thiopyrazole.The reaction was performed using dry acetonitrile as solvent and at atemperature of 0°-5° C. initially and then at ambient temperature for1/2 hour. By proceeding in a similar manner there was obtained:

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)5-iodo-4-trifluoromethylsulphinylpyrazole,m.p. 165°-166° C., in the form of a pale yellow solid; from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphenylpyrazole.

Reference Example 4

3-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole,used in the above Example was prepared as follows:

3-tert-Butoxycarbonylamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(3.45 g) dissolved in dry acetonitrile (80 ml) was treated withiodotrimethylsilane (2.6 g) added dropwise under nitrogen. Afterstirring for 45 minutes, methanol (10 ml) was added, and after a further15 minutes the solution was concentrated in vacuo to give a dark gum.This was dissolved in dichloromethane (100 ml), washed with a solutionof sodium sulphite (50 ml), then with water (50 ml) and dried overanhydrous magnesium sulphate. Evaporation of the dichloromethane gavethe title compound (2.6 g), m.p. 130°-135° C., as an off white solid.

3-tert-Butoxycarbonylamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazoleused above, was prepared as follows:

1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole-3-carboxylicacid (5.6 g) was dissolved in dry N,N-dimethylformamide (50 ml) andtriethylamine (1.33 g) added. After cooling to 5° C., a solution ofdiphenylphosphorylazide (3.63 g) in N,N-dimethylformamide (20 ml) wasadded. When the solution had reached ambient temperature, it was heatedto 35° C. for 21/2 hours. After evaporation in vacuo at a temperaturekept below 40° C., a solution of sodium chloride (5 g) in water (100 ml)was added, and the suspension extracted with ether (3×100 ml). Thecombined extracts were washed with water (50 ml), dried over anhydrousmagnesium sulphate and evaporated to give1-(2,6-dichloro-4-trifluoromethylphenyl)4-trifluoromethylthiopyrazole-3-carboxylicacid azide (5.4 g). A solution of this in dry toluene (200 ml) washeated under reflux with stirring for 1.5 hours, tert-butanol (35 ml)was added, and reflux continued for 4 hours. After evaporation in vacuothe residue was purified by chromatography eluting with dichloromethaneto give the title compound (3.3 g) as an off-white solid, m.p. 122°-125°C.

1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole-3-carboxylicacid used above, was prepared as follows:

A solution of sodium hydroxide (1.73 g) in water (50 ml) was added to asuspension of1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-trifluoromethylthiopyrazole(6.8 g) in ethanol (70 ml), and the mixture heated under reflux for 11/2hours. The solvent was evaporated in vacuo, water (250 ml) added,followed by concentrated sulphuric acid to pH1. The product was filteredoff, washed with water (100 ml) and dried at 120° C. in vacuo giving thetitle compound (5.7 g) as a grey solid, m.p. 175°-177° C.

1-(2,6-Dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-trifluoromethylthiopyrazoleused above, was prepared by following the procedure of Example 8 byreplacing the5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazoleby5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-trifluoromethylthiopyrazole.The title compound was obtained as an off white solid, m.p. 125.5°-126°C.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-trifluoromethylthiopyrazoleused above, was prepared by the procedure described in Example 1, andobtained in the form of a white solid, m.p. 213°-214° C. afterpurification by chromatography; from5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)3-ethoxycarbonylpyrazole.5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonylpyrazolewas prepared as follows:

A solution of 3-cyano-2-hydroxyprop-2-enoic acid ethyl ester sodium salt(50.0 g) [C.A.57:16604d N. S. Vulfson et al] in cold water (500 ml) wasstirred whilst cold sulphuric acid (2N) was added to pH1. The solutionwas extracted with ether (2×400 ml) and the extract washed with water(200 ml), dried over anhydrous magnesium sulphate, and evaporated invacuo to give a yellow oil (29.4 g). A solution of this in ethanol (400ml) was treated with 2,6-dichloro-4-trifluoromethylphenylhydrazine (51.1g), and the solution heated under reflux overnight. After cooling, thesolution was evaporated in vacuo to give an orange solid.Recrystallisation from toluene/hexane gave the title compound as a fawnsolid (40.2 g), m.p. 179°-181° C.

EXAMPLE 10 Compounds Nos. 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61,62, 91

A partial solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(48.0 g) in chloroform (600 ml) was stirred mechanically and treatedwith m-chloroperbenzoic acid (61.4 g). The mixture was stirred andheated under reflux in an atmosphere of nitrogen for 3.5 hours. Aftercooling, an additional amount of m-chloroperbenzoic acid (12.3 g) wasadded, and reflux continued for 1 hour. The cooled mixture was dilutedwith ethyl acetate (600 ml), washed with a solution of sodiummetabisulphite (2×250 ml), then with sodium hydroxide solution (2×250ml) and finally with water (1×500 ml). The organic layer was dried overanhydrous magnesium sulphate, filtered, and evaporated in vacuo to givea fawn solid.

Recrystallisation from toluene/hexane/ethyl acetate gave5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethanesulphonylpyrazoleas white crystals (37.0 g) m.p. 219°-221.5° C.

A stirred solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(10.0 g) in dichloromethane (100 ml) was treated with m-chloroperbenzoicacid (4.5 g). After stirring overnight additional m-chloroperbenzoicacid (1.6 g) was added in 2 portions, and left for 2 days. The reactionproduct was diluted with ethyl acetate (30 ml) and then washed in turnwith sodium sulphite solution (50 ml), sodium carbonate solution (50 ml)and with water (50 ml). After drying over magnesium sulphate, this wasfiltered and evaporated in vacuo. Purification by chromatography onsilica eluting with dichloromethane gave5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphinylpyrazoleas a white solid (6.0 g), m.p. 200.5°-201° C.

By proceeding in a similar manner and by replacing the abovementionedphenylpyrazoles by the appropriate phenylpyrazoles there was prepared:

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-trifluoromethanesulphonylpyrazole,m.p. 210°-211.5° C., in the form of a white solid, and5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-trifluoromethylsulphinylpyrazole,m.p.179°-180° C., in the form of a white solid.

Both of the above two compounds being prepared from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-trifluoromethylthiopyrazoleby the use of an appropriate quantity of m-chloroperbenzoic acid.

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphinylpyrazole,m.p. 142.5°-144.2° C., in the form of a white solid, from3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazoleand by performing the reaction at 40°-50° C. for 20 hours.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(1-methylprop-2-ynylsulphinyl)pyrazole,136.6°-137.2° C., in the form of a white solid, from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(1-methylprop-2-ynylthio)pyrazole.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylsulphinylpyrazole,m.p. 176°-177° C., in the form of a fawn crystalline solid; preparedfrom5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthiopyrazole.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-isopropylsulphinylpyrazole,m.p. 187°-188° C., in the form of a white solid; prepared from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-isopropylthiopyrazole.

5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphinylpyrazole,m.p. 179°-180° C., in the form of a white solid; prepared from5-amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole.

5-Amino-4-tert-butanesulphonyl-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole,m.p. 183°-184° C., in the form of a pale yellow solid; prepared from5-amino-4-tert-butylthio-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazoleemploying 2 molar equivalents of m-chloroperbenzoic acid in chloroformand at room temperature for 4 hours.

By proceeding in a similar manner there was prepared:

5-Amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluromethanesulphonylpyrazole,m.p. 162°-164° C., in the form of a white solid, from5-amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)4-trifluoromethylthiopyrazole.

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-propylamino-4-trifluoromethanesulphonylpyrazole,m.p. 49°-65° C., in the form of a yellow solid; prepared from3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-propylamino-4-trifluoromethylthiopyrazoleat room temperature.

5-Acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethanesulphonylpyrazole,m.p. 174°-175.9° C., in the form of a white solid; prepared from5-acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylthiopyrazoleemploying 2 molar equivalents of m-chloroperbenzoic acid and heatingunder reflux in chloroform for 20 hours.

EXAMPLE 11 Compounds Nos. 63, 64

Trifluoroacetic anhydride (6.0 ml) was added dropwise during 15 minutesto a stirred mixture of 85% hydrogen peroxide (0.96 ml) indichloromethane (20 ml) at 0°-10° C. The mixture was warmed to 20° C.for 5 minutes, and a suspension of3-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole(2.0 g) in dichloromethane (20 ml) was added during 5 minutes. Thesolution was then heated under reflux for 1 hour and left at roomtemperature overnight. This was poured onto water (100 ml) and theorganic layer washed in turn with sodium metabisulphite solution (30 ml)and sodium bicarbonate solution (30 ml), and then dried over anhydrousmagnesium sulphate. Evaporation in vacuo gave, after recrystallizationfrom dichlormethane/toluene/hexane,1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-nitropyrazole,m.p. 190°-192° C., in the form of a white solid.

By proceeding in a similar manner but replacing the3-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazoleby3,5-diamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazolethere was prepared:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-nitropyrazolein the form of a cream solid, m.p. 190°-192° C. The oxidation wasperformed initially at 0° C. and then warmed to room temperature for 1.5hours. Purification by chromatography eluting with dichloromethane, andrecrystallisation from toluene was necessary in this case.

EXAMPLE 12 Compound No. 65

A stirred mixture of 85% hydrogen peroxide(0.31 g) and dichloromethane(20 ml) was treated with trifluoroacetic anhydride (2.1 g) dropwise at-10° C. After 15 minutes the mixture was allowed to reach roomtemperature, and stirred for a further 15 minutes. After re-cooling to0° C., a solution of3-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(1.0 g) [preparation described in Reference Example 4] indichloromethane (20 ml) was added, and the solution allowed to warm toroom temperature. After 2 hours, an additional quantity oftrifluoroperacetic acid [prepared as above using 85% hydrogen peroxide(0.31 g); dichloromethane (20 ml) and trifluoroacetic anhydride (2.1 g)]was added. The mixture was stirred overnight, then poured onto water (50ml), and the dichloromethane layer washed in turn with 5% sodiumsulphite solution (30 ml), sodium bicarbonate solution (30 ml) and withwater (30 ml). This solution was then dried over anhydrous magnesiumsulphate, and evaporated in vacuo to give a green gum (0.8 g).Purification by chromatography eluting with dichloromethane/hexane (3:2)gave1-(2,6-dichloro-4-trifluoromethylphenyl)-3-nitro-4-trifluoromethyl-sulphinylpyrazole(0.3 g), m.p. 124°-130° C., in the form of a pale green solid.

EXAMPLE 13 Compounds Nos. 66, 67

Phosphorus oxychloride (20 ml) was added to5-amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-3-carbamoyl-4-methanesulphonylpyrazole(4.0 g) and the solution heated at 50°-60° C. for 3.25 hours, and leftat room temperature overnight. The mixture was cautiously added tovigorously stirred water (200 ml), and the precipitated solid collectedand dried in vacuo. Recrystallisation from toluene/ethanol gave5-amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-3-cyano-4-methanesulphonylpyrazoleas buff crystals, m.p. 235°-238° C.

By proceeding in a similar manner to that described above but replacingthe5-amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-3-carbamoyl-4-methylsulphonylpyrazoleby5-amino-3-carbamoyl-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-methanesulphonylpyrazolethere was obtained:

5-Amino-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-3-cyano-4-methanesulphonylpyrazolein the form of a white solid, m.p. 202.5°-203.5° C.

Reference Example 5

5-Amino-3-carbamoyl-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-methanesulphonylpyrazole,used above, was prepared as follows:

As suspension of5-amino-3-carboxy-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-methanesulphonylpyrazole(40.0 g) in toluene (160 ml) was treated with thionyl chloride (150 ml)and the mixture heated under reflux with stirring for 3 hours. Thesolution was evaporated in vacuo and reevaporated after addition oftoluene (100 ml). The resultant acid chloride was dissolved intetrahydrofuran (200 ml) and this solution added dropwise during 15minutes to stirred ammonia solution (300 ml), with cooling at 5°-10° C.throughout. After standing overnight, water (250 ml) was added and thesolution extracted with ethyl acetate (3×100 ml). The combined extractwas washed with water (2×250 ml), dried over anhydrous magnesiumsulphate, and evaporated in vacuo to give a solid (34.9 g). The titlecompound (19.3 g) was obtained in the form of a white solid, m.p.219°-220° C., after recrystallisation from ethyl acetate/hexane.

By proceeding in a similar manner but replacing the5-amino-3-carboxy-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-methanesulphonylpyrazoleby5-amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)3-carboxy-4-methanesulphonylpyrazolethere was obtained:

5-Amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-3-carbamoyl-4-methanesulphonylpyrazole,m.p. 250°-253° C., in the form of a grey-brown powder.

5-Amino-3-carboxy-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-methanesulphonylpyrazole,used above, was prepared by using the method employed to prepare3-carboxy-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazoleby replacing the1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethoxycarbonyl-4-methanesulphonylpyrazole(Reference Example 3) by5-amino-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-3-ethoxycarbonyl-4-methanesulphonylpyrazole.It was obtained in the form of a white solid, m.p. 195°-196° C.

5-Amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-3-carboxy-4-methanesulphonylpyrazole,used above, was prepared as follows:

5-Amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-methanesulphonylpyrazole(8.0 g) was heated under reflux with 48% hydrobromic acid (75 ml) inacetic acid (75 ml) for 3 hours. After cooling overnight, this wasevaporated in vacuo, and the residue triturated with aqueous sodiumbicarbonate. The title compound was obtained as a grey powder (6.6 g),m.p. 130°-133° C., after drying in vacuo.

5-Amino-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-3-ethoxycarbonyl-4-methanesulphonylpyrazole,used above, was prepared by the procedure of Reference Example 3 byreplacing ethyl chloro(2,6-dichloro-4-trifluoromethylphenyl)hydrazonoacetate by ethyl chloro(2,6-dichloro-4-trifluoromethoxyphenyl)hydrazonoacetate. It was obtainedin the form of a light brown solid, m.p. 207° C.

5-Amino-1-(2-bromo-6-chloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-methanesulphonylpyrazole,used above, was prepared similarly from ethyl chloro(2-bromo-6-chloro-4-trifluoromethylphenyl)hydrazonoacetate. It wasobtained as a white solid, m.p. 255.5°-256.5° C.

Ethyl chloro (2,6-dichloro-4-trifluoromethoxyphenyl)hydrazonoacetate,used above, was prepared by the procedure of Reference Example 3 byreplacing 2,6-dichloro-4-trifluoromethylaniline by2,6-dichloro-4-trifluoromethoxyaniline, and was obtained as a brownsolid, m.p. 55°-58° C.

Ethyl chloro (2-bromo-6-chloro-4-trifluoromethylphenyl)hydrazonoacetate,used above, was prepared similarly from2-bromo-6-chloro-4-trifluoromethylaniline, and was obtained as a buffsolid, m.p. 116.5°-117.5° C.

EXAMPLE 14 Compound No. 68

A solution of sodium ethoxide prepared from sodium (0.36 g) and absoluteethanol (50 ml) was treated at room temperature with methanesulphonylacetonitrile (1.88 g) and stirred for 1 hour. To this was then addeddropwise with stirring, a solution of1-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)hydrazonopropan-2-one(5.0 g) in ether (50 ml). After stirring overnight the solution wasdiluted with water (100 ml), extracted with ether (3×50 ml), and thecombined ethereal extracts dried over anhydrous magnesium sulphate, andevaporated in vacuo to give a brown solid.

Recrystallisation from toluene/hexane gave3-acetyl-5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole(2.56 g) in the form of a buff solid, m.p. 176.7°-178.9° C.

1-Chloro-1-(2,6-dichloro-4-trifluoromethylphenyl) hydrazonopropan-2-one,used above, was prepared by the procedure described in Reference Example3, but replacing the ethyl chloroacetoacetate by3-chloropentan-2,4-dione. It was obtained in the form of a light brownsolid, m.p. 77°-79° C., after recrystallisation from petroleum etherb.p. 60°-80° C.

EXAMPLE 15 Compounds Nos. 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 100

A solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-thiocyanatopyrazole(3.1 g) in methanol (50 ml) was stirred under nitrogen at -7° C. andmethyl iodide (5.25 ml) added. A solution of potassium hydroxide (0.92g) in water (10 ml) was then added dropwise during 10 minutes, keepingthe mixture below 0° C. After stirring at room temperature for 3 hours,the mixture was neutralised by the addition of carbon dioxide pellets,followed by water (180 ml). The precipitated solid was filtered off, andrecrystallised from toluene/hexane (2:1).

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthiopyrazolewas obtained as a brown crystalline solid (1.94 g), m.p. 170°-172° C.

By proceeding in a similar manner but replacing the methyl iodide by thefollowing alkyl halides there was obtained:

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthiopyrazolein the form of a yellow solid, m.p. 158°-160° C., by using ethyl iodideand aqueous ethanol as solvent.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-propylthiopyrazolein the form of a pale brown solid, m.p. 123°-124° C., by using propylbromide and aqueous dioxan as solvent.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-isopropylthiopyrazolein the form of a pale brown solid, m.p. 168°-169° C., by using isopropylbromide and aqueous isopropyl alcohol as solvent.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(2-methylpropylthio)pyrazolein the form of a pale brown solid, m.p. 134°-137° C., by using1-iodo-2-methylpropane and aqueous dioxan as solvent.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(1-methylpropylthio)pyrazolein the form of a pale brown solid, m.p. 152.5°-154° C., by using2-iodobutane and aqueous dioxan as solvent. The product was purified bydry column chromatography on silica eluting with hexane/diethylether(1:1).4-Allylthio-5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazolein the form of a pale brown solid, m.p. 140°-141° C., by using allylbromide and aqueous dioxan as solvent. The product was purified bychromatography eluting with hexane/diethyl ether (1:1), followed byrecrystallisation from toluene.5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(prop-2-ynylthio)pyrazolein the form of a brown solid, m.p. 161°-163° C., by using propargylbromide and aqueous methanol as solvent.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(1-methylprop-2-ynylthio)pyrazolein the form of a white solid, m.p. 134°-135.6° C., by using3-bromobut-1-yne and aqueous methanol as solvent. The product waspurified by chromatography eluting with diethyl ether/hexane (1:1),followed by recrystallisation from toluene/hexane.

5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl-4-methylthiopyrazolein the form of a white solid, m.p. 117°-119° C., by using methyl iodideand aqueous methanol as solvent. The product was purified bychromatography eluting with dichloromethane.

By proceeding in a similar manner there was prepared:

5-Amino-4-(2-chloro-1,1,2-trifluoroethylthio)-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole,m.p. 116°-118° C., in the form of a white solid, by usingchlorotrifluoroethylene and aqueous dioxan as solvent. The product waspurified by chromatography eluting with dichloromethane, and subsequentrecrystallisation from toluene/hexane (3:10).

Reference Example 6

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-thiocyanatopyrazole,used above, was prepared as follows:

A suspension of potassium thiocyanate (4.99 g) in methanol (75 ml) wasstirred at -78° C. Bromine (0.8 ml) dissolved in methanol (10 ml) wasthen added dropwise during 25 minutes. After a further 20 minutes, asolution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole (5.0 g)in methanol (50 ml) was then added over 30 minutes. The mixture wasstirred at -78° C. and then allowed to warm to room temperature for 3hours, before pouring onto water (250 ml). The precipitated solid wasfiltered off, washed with water, and recrystallised from toluene/hexaneto give the title compound (3.1 g) as a white solid, m.p. 179°-182° C.

By proceeding in a similar manner but replacing the5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole in theabove Reference Example by5-amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole, therewas obtained:

5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-thiocyanatopyrazolein the form of a white solid, m.p. 162°-163.5° C., after purification bychromatography, eluting with dichloromethane. The preparation of5-amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole, usedabove, is described in Reference Example 1.

EXAMPLE 16 Compound No. 79

To a stirred solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-thiocyanatopyrazole(5.0 g) in dry diethyl ether (70 ml) at 0° C. under an atmosphere ofnitrogen, was added dropwise a solution of tert-butylmagnesium chloride(7.92 ml of a 2M solution in dry ether). The solution was then allowedto reach room temperature, and the stirring continued for 3 hours. Water(40 ml) was then added and the mixture stirred for 15 minutes. Theethereal layer was separated, washed with water (50 ml), dried overanhydrous magnesium sulphate, and evaporated in vacuo to give a brownsolid. Purification by chromatography eluting withdichloromethane/petroleum ether (3:1) gave5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-tert-butylthiopyrazole(2.62 g), m.p. 196°-198.5° C., in the form of a pale yellow solid.

EXAMPLE 17 Compounds Nos. 80, 81

A solution of5-amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthiopyrazole(2.0 g) [preparation described in Example 15] in methanol (45 ml) at-25° C. was treated with a rapidly added solution of potassium hydrogenpersulphate (1.66 g), followed immediately by the addition of water (22ml). The mixture was stirred for 30 minutes at 0° C., and potassiumhydrogen persulphate (0.4 g) added. After 21/2 hours stirring at roomtemperature, the mixture was poured onto water (300 ml) and saturatedsodium bisulphite solution (35 ml) added. This was extracted withdichloromethane (2×150 ml) and the extract washed with water (2×50 ml),dried over anhydrous magnesium sulphate, and evaporated in vacuo. Thecrude product was purified by chromatography eluting withdichloromethane/ethyl acetate (4:1) to give5-amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylsulphinylpyrazole(0.9 g) as a white solid, m.p. 135°-136° C.

By proceeding in a similar manner but replacing the5-amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthiopyrazoleby5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)4-ethylthiopyrazoleand by utilising an appropriate quantity of potassium hydrogenpersulphate there was obtained:

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethanesulphonylpyrazolein the form of a yellow solid, m.p. 180°-183° C. In this case thereaction mixture was kept at room temperature for 20 hours, and gave thetitle compound without chromatographic purification.

EXAMPLE 18 Compound No. 82

A solution of3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxymethyleneamino-4-trifluoromethylthiopyrazole(1.7 g) in methanol (30 ml) was stirred, and sodium borohydride (1.08 g)added portionwise. The solution was allowed to reach room temperature,and after a further 7 hours was poured onto water (200 ml). This wasextracted with dichloromethane (3×50 ml), dried over anhydrous magnesiumsulphate, and evaporated in vacuo to give a white solid (1.4 g).Purification by chromatography eluting with dichloromethane/petroleumether (4:1) gave3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methylamino-4-trifluoromethylthiopyrazole(0.42 g) in the form of a white solid, m.p. 208.5°-209.5° C.

EXAMPLE 19 Compound No. 83

To a solution of3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonylamino-4-trifluoromethylthiopyrazole(1.0 g) in dry tetrahydrofuran (20 ml) was added sodium hydride (0.095g) with stirring at 0°-10° C. After stirring at room temperature for21/2 hours, methyl iodide (0.6 g) was added dropwise with cooling at0°-10° C., and the mixture stirred overnight. Additional methyl iodide(0.6 g) was added and stirring continued for 81/2 hours. The solutionwas poured onto water (100 ml) and extracted with dichloromethane (2×50ml).

The extracts were dried over anhydrous magnesium sulphate and evaporatedin vacuo to give3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(N-ethoxycarbonyl-N-methyl)amino-4-trifluoromethylthiopyrazole(0.81 g), m.p. 86.2°-88.5° C., in the form of a white solid.

EXAMPLE 20 Compound No. 84

A mixture of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(3.0 g) and trifluoroacetic anhydride (15.0 g) in tetrahydrofuran (25ml) was heated under reflux for 6 hours. After standing overnight themixture was evaporated in vacuo, dissolved in dichloromethane (50 ml)and washed with sodium bicarbonate solution (50 ml) and with water (50ml). The solution was dried over anhydrous magnesium sulphate andevaporated in vacuo to give a brown oil (2.9 g). Trituration with hexanethen gave3-cyano-1-(2,6-dichloro-4-trifluozomethylphenyl)-5-trifluoroacetamido-4-trifluoromethylthiopyrazole(1.86 g), m.p. 138.2°-139.8° C., in the form of a white solid.

EXAMPLE 21 Compounds Nos. 85, 98

A solution of3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bisethoxycarbonyl)amino-4-trifluoromethylthiopyrazole(1.8 g) in ethanol (20 ml) was treated with a saturated solution ofsodium bicarbonate (20 ml), and the mixture heated under reflux for 11/2hours. After evaporation in vacuo the yellow oil was distributed betweendichloromethane (70 ml) and water (70 ml). The aqueous layer wasre-extracted with dichloromethane (50 ml) and the combined organicsolution dried over anhydrous magnesium sulphate, and evaporated invacuo. Trituration with hexane then gave3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonylamino-4-trifluoromethylthiopyrazole(1.23 g), m.p. 108.7°-109.7° C., in the form of a white solid.

By proceeding in a similar manner there was prepared from3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-4-trifluoromethylsulphonylpyrazole:

3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonylamino-4-trifluoromethylsulphonylpyrazole,m.p. 112.4°-113° C., in the form of a white solid, and afterpurification by chromatography eluting with dichloromethane/hexane(1:1).

EXAMPLE 22 Compound No. 86

To a solution of1-(2,6-dichloro-4-trifluoromethylphenyl)-3-(1-hydroxyethyl)-4-trifluoromethylthiopyrazole(1.1 g) in dichloromethane (40ml) was added pyridinium chlorochromate(0.62 g), and the mixture stirred at room temperature overnight. Ether(50 ml) was added and the mixture filtered on diatomaceous earth.Evaporation of the filtrate in vacuo gave a brown solid, which wastriturated with hexane and filtered. The filtrate was evaporated invacuo to give a yellow solid, which recrystallised from cyclohexane togive3-acetyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(0.4 g) in the form of a yellow solid, m.p. 89°-91° C.

Reference Example 7

1-(2,6-Dichloro-4-trifluoromethylphenyl)3-(1-hydroxyethyl)-4-trifluoromethylthiopyrazoleused in the above Example was prepared as follows: A stirred solution of1-(2,6-dichloro-4-trifluoromethylphenyl)-3-formyl-4-trifluoromethylthiopyrazole(1.64 g) in dry ether (20 ml) was treated with a solution of methylmagnesium iodide (1.35 ml of a 3M solution in ether) added dropwiseduring 5 minutes under nitrogen. The solution was then heated underreflux for 11/2 hours, after which time it was cooled and treated withan additional portion of methyl magnesium iodide solution (0.2 ml) inthe same manner as before. After another 1 hour of reflux, the mixturewas poured onto excess ice and dilute hydrochloric acid (100 ml) andextracted with ether (2×50 ml). The extract was washed with sodiumbicarbonate solution (50 ml), and with water (50 ml) and dried overanhydrous magnesium sulphate. Evaporation in vacuo gave the titlecompound (1.46 g), in the form of a yellow oil.

EXAMPLE 23 Compound No. 87

A stirred solution of3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(2.03 g) in dry tetrahydrofuran (20 ml) was treated with a solution ofdiisobutyl aluminium hydride (10 ml of a 1.0M solution in toluene) whichwas added dropwise under nitrogen at -60° to 70° C. during 10 minutes.The solution was allowed to warm to room temperature for 3 hours andthen at -10° C. overnight. After pouring onto ice and 2N sulphuric acid(100 ml) and stirring for 1/2 hour, the mixture was extracted intodichloromethane (3×25 ml). The extract was washed with water (50 ml),dried over anhydrous magnesium sulphate, and evaporated in vacuo to givea yellow oil (1.8 g). Purification by chromatography eluting withdichloromethane/hexane (1:1) gave1-(2,6-dichloro-4-trifluoromethylphenyl)-3-formyl-4-trifluoromethylthiopyrazole(1.5 g) in the form of a white solid, m.p. 79°-81° C.

EXAMPLE 24 Compound No. 88

A solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole(2.0 g) in formic acid (90%, 50 ml) was heated under reflux with Raneynickel (2.0 g), cooled and heating continued for 5 hours after a furtheraddition of Raney nickel (2.0 g). The filtered mixture was diluted withwater (250 ml) and extracted with dichloromethane (4×50 ml). The extractwas washed with sodium bicarbonate solution (2×50 ml), dried overanhydrous magnesium sulphate, and evaporated in vacuo to give a solid(1.0 g). Purification by chromatography eluting with dichloromethanegave5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-formyl-4-trifluoromethylthiopyrazole(0.05 g), m.p. 140°-143° C., in the form of yellow crystals, afterrecrystallisation from toluene/hexane.

EXAMPLE 25 Compound No. 89

A mixture of dry sulpholane (15 ml) and 4Å molecular sieve (3.0 g) wasstirred under nitrogen with caesium fluoride (2.4 g) at 60° C. for 1,2hour. To this was added5-bromo-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethanesulphonylpyrazole(2.0 g) and the mixture stirred at 60° C. for 2 hours, and leftovernight at room temperature. This was diluted with ether (50 ml),filtered, and washed with water (100ml). The aqueous layer wasreextracted with ether (3×50 ml) and the combined organic solutionre-washed with water (4×50ml), dried over anhydrous magnesium sulphate,and evaporated in vacuo to give an oil. Purification by chromatography,eluting with ether/hexane (1:4) gave3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-fluoro-4-trifluoromethanesulphonylpyrazole(0.17 g), m.p. 95°-98° C., in the form of a white solid, afterrecrystallisation from hexane.

EXAMPLE 26 Compound No. 92

A solution of pentafluoroethyl iodide (5.0 g) in dry ether (30 ml) wasstirred at -78° C., whilst a solution of phenylmagnesium bromide (0.02mol) in dry ether (20 ml) and a separate solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-thiocyanatopyrazole(7.6 g) in dry ether (75 ml) were added simultaneously dropwise during2.5 hours. The mixture was allowed to reach room temperature, and aftera further 0.5 hour, was treated with a solution of hydrochloric acid(2M, 15 ml) at 0° C. The ethereal layer was dried over anhydrousmagnesium sulphate, and evaporated in vacuo to give a brown gum (8.8 g).Purification by dry column flash chromatography eluting withdichloromethane/-petroleum ether (1:1) gave5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-pentafluoroethylthiopyrazole,m.p. 134.5°-136.5° C.,, in the form of a yellow solid.

EXAMPLE 27 Compound No. 101

To a solution of5-bromo-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulphonylpyrazole(1.5 g) in dioxan (20 ml) there was added 1,1-dimethylhydrazine (0.62 g)and the mixture heated to 60° C. for 4.25 hours. After pouring ontowater (20 ml) the aqueous layer was extracted with dichloromethane (2×50ml) and this extract combined with the dioxan layer, washed with water(1×50 ml) dried over anhydrous magnesium sulphate, and evaporated invacuo to give a solid (1.4 g). Purification by chromatography elutingwith dichloromethane/hexane (1:1) gave3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dimethylamino-4-trifluoromethylsulphonylpyrazole(0.35 g), m.p. 178°-179° C., in the form of a white solid.

EXAMPLE 28 Compounds Nos 1, 13 and Intermediate in Reference Example 4

To a stirred solution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole (2.23g) and pyridine (0.55 g) in chloroform (50 ml) was added dropwise at 0°C., a solution of trifluoromethylsulphenyl chloride (1.24 g) inchloroform (15 ml) during 20 minutes. The mixture was stirred at 0° C.for 3 hours, and the solvent evaporated in vacuo to give a yellow solid(3.1 g). This was purified by chromatography on silica (Merck, 230-400mesh, 0.7 kgcm⁻²) eluting with dichloromethane and petroleum ether b.40°-60° (3:1) to give5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazolein the form of a white solid (2.33 g), m.p. 169.5°-170.5° C.

By proceeding in a similar manner to that described above but replacingthe 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyanopyrazole bythe following phenylpyrazoles there was obtained:

5-Amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazolein the form of a colourless solid, m.p. 154.5°-156° C., from5-amino-3-bromo-1(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole-3-carboxylicacid ethyl ester in the form of a white solid, m.p. 213°-215° C. from5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl-3-ethoxycarbonylpyrazole.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonylpyrazoleused in the above example was prepared as follows:

A solution of 3-cyano-2-hydroxyprop-2-enoic acid ethyl ester sodium salt(50.0 g) in cold water (500 ml) was stirred and acidified to pH 1 withcold dilute sulphuric acid. Sodium chloride (50 g) was added and thesolution extracted with ether (2×200 ml). This extract was washed withwater (50 ml), dried (anhydrous magnesium sulphate), and evaporated togive a yellow liquid (30.2 g). This was dissolved in ethanol (400 ml)and stirred whilst 2,6-dichloro-4-trifluoromethylphenylhydrazine (51.5g) was quickly added. The solution was then heated under refluxovernight, cooled, and evaporated in vacuo to give an orange solid.After trituration with hexane (300 ml), the filtered solid wasrecrystallized from toluene-hexane with charcoaling to give the titlecompound (43.4 g), m.p. 177°-179° C. as buff crystals.

Reference Example 8

A solution of 2,6-dichloro-4-trifluoromethylphenylhydrazine (10.1 g) intetrahydrofuran (50 ml) was stirred at room temperature, and potassiumcarbonate (anhydrous, 8.5 g) added. To this was added, dropwise at 0°C., a solution of2-chloro-3-cyano-3-(1-methyl)ethylsulphonyl-prop-2-enoic acid ethylester (11.0 g) in tetrahydrofuran (100 ml). After stirring for 2 hours,the mixture was filtered, and the filtrate evaporated in vacuo to give abrown oil. After trituration with hexane (100 ml) this gave an off whitesolid (11.7 g). After refluxing this in ethanol and cooling there wasobtained5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-(1-methyl)ethylsulphonylpyrazole (8.5 g), m.p. 255.5°-256.5° C. as white crystals.

Reference Example 9

2-Chloro-3-cyano-3-(1-methyl)ethylsulphonylprop-2-enoic acid ethyl esterused above was prepared as follows:

3-Cyano-2-hydroxy-3-(1-methyl)ethylsulphonylprop-2-enoic acid ethylester sodium salt (10.0 g) was added to the stirred phosphorusoxychloride (28.5 g) at room temperature. After 3 hours, the mixture washeated at 50° C. for 1 hour, and then-evaporated in vacuo. The residuewas re-evaporated after addition of toluene to give the title compoundas a brown oil.

3-Cyano-2-hydroxy-3-(1-methyl) ethylsulphonylprop-2-enoic acid ethylester sodium salt was prepared as follows:

A solution of sodium ethoxide prepared from sodium (4.0 g) and ethanol(80 ml) was treated with propane-2-sulphonylacetonitrile (24.5 g) withstirring. After complete dissolution diethyl oxalate (24.8 g) was addeddropwise over 10 minutes giving a heavy precipitate. After heating underreflux for 1 hour, the yellow solid was filtered, washed with hexane,and dried in a vacuum dessicator (41.3 g). This was the title compound,m.p. 195°-197.50C.

EXAMPLE 29 Compounds Nos. 59 and 52 and an Intermediate for No. 52

By proceeding in a similar manner to that described below but replacing5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthio-3-trifluoromethylpyrazoleby the following phenylpyrazoles, there was obtained:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-trifluoromethylsulphinylpyrazoleas an off white solid, m.p. 210°-214° C. from5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-trifluoromethylthiopyrazole.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-bromo-4-trifluoromethylsulphinylpyrazolein the form of a white solid, m.p. 179°-180° C. from5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-bromo-4-trifluoromethylthiopyrazole.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulphinylpyrazolein the form of a white solid, m.p. 203°-203.5° C. from5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole.

A stirred solution of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthio-3-trifluoromethylpyrazole(1.0 g) in chloroform (40 ml) was treated with m-chloroperbenzoic acid(0.42 g), portionwise at room temperature. After stirring for 6 hours,the solution was diluted with dichloromethane and washed in turn withsodium sulphite solution, sodium hydroxide solution, and water. Thesolution was dried over anhydrous magnesium sulphate, and evaporated invacuo to give a yellow oil. Purification by chromatography on silica(Merck, 230°-400 mesh, 0.7 kg cm⁻²) eluting withdichloromethane-ethylacetate (4:1) gave5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylsulphinyl-3-trifluoromethylpyrazolein the form of a white solid, m.p. 142°-145° C. with decomposition.

Reference Example 10

5-Carbamoyl-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(3.57 g) was heated to 200° C. with phosphorus pentoxide (2.82 g) withstirring. After 3 hours, the cooled product was treated with ice, andextracted with dichloromethane (3×50 ml). The organic solution waswashed with water, dried over anhydrous magnesium sulphate, andevaporated in vacuo to give a solid. Recrystallization from hexane gave1-(2,6-dichloro-4-trifluoromethylphenyl)-4,5-dicyano-3-trifluoromethylpyrazolein the form of white crystals (1.8 g), m.p. 80° C.

By proceeding in a similar manner to that described above but replacethe5-carbamoyl-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby5-amino-3-carbamoyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazolethere wasprepared:-5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazolein the form of a white solid, m.p. 214° C.

Reference Example 11

5-Carbamoyl-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleused in the above Reference Example 10, was prepared as follows:

5-Carboxy-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(6.0 g) was added to thionyl chloride (30 ml) and the stirred,.solutionheated to reflux for 4 hours. The solvent was evaporated in vacuo, andre-evaporated after addition of dry toluene (30 ml). The resultantorange oil was dissolved in dry ether (10 ml) and added dropwise to astirred solution of ammonia (0.88, 20 ml) cooled by an ice bath. Afterstirring overnight, water (150 ml) was added, and the mixture extractedwith dichloromethane (3×50 ml). The combined extract was washed withwater, dried over anhydrous magnesium sulphate, and evaporated in vacuoto give a white solid (7.0 g). Recrystallization from a mixture of ethylacetate and petroleum ether gave the title compound (4.3 g), in the formof white crystals, m.p. 180°-181° C.

5-Amino-3-carbamoyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazoleused in the above Reference Example 10 was prepared by the sameprocedure, but by replace the5-carboxy-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby5-amino-3-carboxy-1-(2,6-dichloro-4-trifluoromethylphenyl-4-methanesulphonylpyrazole.The title compound was obtained in the form of an off-white solid, m.p.223°-224° C.

5-Amino-3-carboxy-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazoleused above was prepared as follows:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-methanesulphonylpyrazole(8.15 g; Reference Example 3) was added to stirred 80% sulphuric acid(80 ml), and heated at 100° C. for 5 hours. After cooling, the solutionwas poured onto ice, the solid filtered off and dried over phosphoruspentoxide in a vacuum desiccator. Recrystallization from a mixture ofmethanol and petroleum ether gave the title compound as a white solid,m.p. 203°-205° C.

Processes for producing compounds of the second embodiment of theinvention, wherein the various substituents are as defined above for thesecond embodiment, are described hereinafter According to processversion "aa", which is a further feature of the present invention,compounds of the second embodiment of the invention, having formulaXXVI, wherein R³ represents an amino group --NHR'"^(a), wherein R'"^(a)represents the hydrogen atom or a straight- or branched-chain alkylgroup containing from 1 to 6 carbon atoms may be prepared from compoundsof formula XXVI, wherein R³ represents an amino group --NR"^(a) R'"^(b),wherein R"^(a) represents the formyl group or a straight- orbranched-chain alkanoyl group containing from 2 to 7 carbon atoms whichmay be unsubstituted or substituted by one or more halogen atoms, or astraight- or branched-chain alkoxycarbonyl group containing from 2 to 7carbon atoms, which may be unsubstituted or substituted by one or morehalogen atoms, and R'"^(b) is as hereinbefore defined for R'" exceptthat R"^(a) and R'"^(b) together do not form a 5 or 6 membered cyclicimide with the nitrogen atom to which they are attached, by hydrolysis.The hydrolysis is generally effected with an acid such as hydrochloricacid or hydrobromic acid in a solvent such as acetic acid or dioxan, orwith an alkali metal, e.g. sodium or potassium, hydroxide in water or aninert organic or aqueous-organic solvent, e.g. a lower alkanol such asmethanol or a mixture of water and a lower alkanol, at a temperaturefrom laboratory temperature to the boiling point of the reactionmixture.

According to process version "bb", which is a further feature of thepresent invention, compounds of formula XXVI, wherein R³ is ashereinbefore defined but does not represent an unsubstituted amino oralkylamino group, may be prepared from the corresponding compoundswithin formula XXVII, wherein R¹, R⁴, R⁶ and R⁸ are as hereinbeforedefined and R³ is replaced by R^(3a) which is as hereinbefore definedfor R³ but does not represent an unsubstituted amino or alkylamino group(such compounds are referred to as of formula XXVIIA), by treatment witha nitrating agent, preferably nitric acid, optionally in the presence ofsulphuric acid, or nitric acid in a solvent such as acetic acid oracetic anhydride, at a temperature from 0° C. to 100° C.

The preparation of derivatives of the 5-amino group form a furtherfeature of the present invention and are collectively referred to asprocess "cc". Compounds of formula XXVI which conform to formula XXVIB,wherein R" represents an R²¹ C(═O)-- group, wherein R²¹ represents astraight- or branched-chain alkyl or alkoxy group containing from 1 to 6carbon atoms which is unsubstituted or substituted by one or morehalogen atoms, and R'" represents a hydrogen atom or an R²¹ C(═O)--group which is identical to the group R²¹ C(═O)-- represented by R", or--NR"R'" represents a cyclic imide as hereinbefore defined, may beprepared by the reaction of a compound of formula XXVI wherein R³represents the unsubstituted amino group, or an alkali metal saltthereof, with a compound of the formula XXVIII:

    R.sup.21 COX.sup.7                                         XXVIII

wherein X⁷ represents a chlorine or bromine atom, or with a compound ofthe formula XXIX:

    (R.sup.21 CO).sub.2 O                                      XXIX

or with a dicarboxylic acid derivative. The reaction may be conducted inthe absence or presence of an inert organic solvent, for exampleacetonitrile, tetrahydrofuran, a ketone, e.g. acetone, an aromatichydrocarbon, e.g. benzene or toluene, chloroform, dichloromethane ordimethylformamide, and optionally in the presence of an acid-bindingagent, for example pyridine, triethylamine or an alkalimetal, e.g.sodium or potassium, carbonate or bicarbonate, at a temperature from 0°C. to the reflux temperature of the reaction medium, to give a compoundof formula XXVIB, wherein R" represents an R²¹ C(═O)-- group wherein R²¹is as hereinbefore defined and R'" represents a hydrogen atom or an R²¹C(═O)-- group, depending upon the reaction conditions chosen and/or theuse of an excess of the compound of formula XXVIII or XXIX, or --NR"R'"represents a cyclic imide as hereinbefore defined.

Compounds of formula XXVIB, wherein R" represents a formyl group and R'"represents a hydrogen atom or a formyl group, may be prepared by thereaction of a compound of formula XXVI, wherein R³ represents theunsubstituted amino group with formylacetic anhydride. Formylaceticanhydride may be prepared from formic acid and acetic anhydride and thereaction with the compound of formula XXVI may be conducted in theabsence or presence of an inert organic solvent, for example a ketone,e.g. acetone, or an aromatic hydrocarbon, e.g. benzene or toluene, andoptionally in the presence of an acid-binding agent, for examplepyridine, triethylamine or an alkali metal, e.g. sodium or potassium,carbonate or bicarbonate, at a temperature from 0° C. to the refluxtemperature of the reaction mixture, to give a compound of formula XXVIBwherein R" represents a formyl group and R'" represents a hydrogen atomor a formyl group, depending upon the reaction conditions chosen and/orthe use of an excess of formylacetic anhydride. .

Compounds of formula XXVIB wherein R" represents a formyl group or agroup R²¹ C(═O)-- and R'" represents a hydrogen atom may be prepared bythe selective removal by hydrolysis of an R²¹ C(═O)-- group or a formylgroup from a compound of formula XXVIB wherein R" and R'" both representa R²¹ C(═O)-- group or a formyl group. Hydrolysis is effected under mildconditions, for example by treatment with an aqueous-ethanolic solutionor suspension of an alkali metal, e.g. sodium or potassium, bicarbonate,or with aqueous ammonia.

Compounds of formula XXVIB, wherein R" represents a straight- orbranched-chain alkoxycarbonyl group containing from 2 to 7 carbon atomswhich is unsubstituted or substituted by one or more halogen atoms, andR'" represents a hydrogen atom may be prepared by the reaction of acompound of the formula XXX wherein R²² represents an alkoxycarbonylgroup R²³ C(═O), wherein R²³ represents a straight- or branched-chainalkoxy group containing from 1 to 6 carbon atoms (which is unsubstitutedor substituted by one or more halogen atoms) or a phenoxy group, with acompound of the formula XXXI:

    R.sup.23 H                                                 XXXI

to replace a first group represented by the symbol R²² by a hydrogenatom, and to replace the second group represented by the symbol R²² byan alkoxycarbonyl group when R²² represents a phenoxycarbonyl group, or,if desired, to replace the second group represented by the symbol R²² byanother alkoxycarbonyl group when R²² in formula XXX represents analkoxycarbonyl group. As will be apparent to those skilled in the art,the desired compound of formula XXVIB is obtained by selection of theappropriate compounds of formulae XXX and XXXI. The reaction may beeffected in water or an inert aqueous organic or organic solvent, forexample an alkanol containing 1 to 4 carbon atoms, e.g. ethanol, or anaromatic hydrocarbon, e.g. benzene or toluene, which is preferably anexcess of the compound of formula XXXI, at a temperature from ambienttemperature to the reflux temperature of the reaction mixture and, ifnecessary, at elevated pressure, and optionally in the presence of abase, for example an alkali metal alkoxide, e.g. of the compound offormula XXXI.

Compounds of formula XXVIB wherein R" and R'", which may be the same ordifferent, each represents a formyl group or a R²¹ C(═O)-- group, may beprepared by the reaction of an alkali metal, e.g. sodium or potassium,derivative of a compound of formula XXVIB wherein R" represents a groupR²¹ C(═O)-- as hereinbefore defined, or a formyl group, and R'"represents a hydrogen atom with formylacetic anhydride or a compound offormula XXVIII. Reaction may be effected in an inert aprotic solvent,e.g. dimethylformamide, at a temperature from laboratory temperature tothe reflux temperature of the reaction mixture.

Alkali metal derivatives of compounds of formula XXVI (wherein R³represents the unsubstituted amino group) or XXVIB wherein R'"represents a hydrogen atom may be prepared in situ by reaction with analkali metal, e.g. sodium or potassium, hydride, in an inert aproticsolvent, e.g. dimethylformamide, at a temperature from laboratorytemperature to the reflux temperature of the reaction mixture.

Compounds of formula XXX wherein R²² represents a group R²³ C(═O)--, maybe prepared as hereinbefore described. Compounds of formula XXX whereinR²² represents a phenoxycarbonyl group may be prepared by the rection ofa compound of formula XXVI (wherein R³ represents the unsubstitutedamino group), with phenyl chloroformate using the reaction conditionshereinbefore described for the reaction of a compound of formula XXVIwith a compound of formula XXVIII.

Compounds of formula XXVIB wherein R" represents a group R²⁴ whichrepresents a straight- or branched-chain alkyl group containing from 1to 6 carbon atoms and R'" represents a hydrogen atom may be prepared bythe removal of the group R²¹ C(═O)-- of a compound of the formula XXVIB,wherein R" represents a group R²⁴ and R'" represents a group R²¹C(═O)--. Removal of the group R²¹ C(═O)-- may be effected by selectivehydrolysis under mild conditions, for example by treatment with analkali metal, e.g. sodium or potassium, hydroxide in water or an inertorganic or aqueous-organic solvent, for example a lower alkanol, e.g.methanol, or a mixture of water and lower alkanol, at a temperature fromlaboratory temperature up to the reflux temperature of the reactionmixture.

Compounds of formula XXVIB, wherein R" represents a group R²⁴ and R'"represents a group R²¹ C(═O)--, may be prepared by reaction of acompound of formula XXVIB, wherein R" represents a hydrogen atom, or analkali metal, e.g. sodium or potassium, derivative thereof, with acompound of the formula XXXII:

    R.sup.24 X.sup.8                                           XXXII

wherein X⁸ represents a chlorine, bromine or iodine atom. Reaction maybe effected in an inert organic solvent, e.g. dichloromethane,tetrahydrofuran, or dimethylformamide, at a temperature from ambient upto the boiling point of the reaction mixture and, when a compound offormula XXVIB is used, in the presence of a base, e.g. Triton B; or byreaction of a compound of formula XXVIB wherein R" represents thehydrogen atom and R'" represents a group R²⁴ with a compound of formulaXXVIII or XXIX.

Compounds of formula XXVI, wherein R³ represents anN-alkyl-N-formylamino group as hereinbefore described may be prepared ina similar manner to the process above using, where appropriate,formylacetic anhydride instead of a compound of formula XXVIII or XXIX.

Compounds of formula XXVIB, wherein one or both of R" and R'" representa straight- or branched-chain alkyl group containing from 1 to 6 carbonatoms, groups represented by R" and R'" being identical, may be preparedby reaction of a compound of formula XXVI, wherein R³ represents theunsubstituted amino group, or an alkali metal, e.g. sodium or potassium,derivative thereof, with a compound of formula XXXII, in the absence orpresence of an inert organic solvent, for example an aromatichydrocarbon, e.g. benzene or toluene, chloroform, dichloromethane,tetrahydrofuran or dimethylformamide, and optionally in the presence ofan acid-binding agent, for example pyridine, triethylamine or an alkalimetal, e.g. sodium or potassium, bicarbonate, at a temperature from 0°C. up to the boiling point of the reaction mixture.

Compounds of formula XXVI, wherein R³ represents a straight- orbranched-chain alkoxymethyleneamino group containing from 2 to 5 carbonatoms which may be unsubstituted or substituted on methylene by astraight- or branched-chain alkyl group containing from 1 to 4 carbonatoms may be prepared by the reaction of a compound of formula XXVI(wherein R³ represents the unsubstituted amino group) with atrisalkoxyalkane in the presence of an acidic catalyst, e.g.p-toluenesulphonic acid, at a temperature from ambient to the boilingpoint of the reaction mixture.

Compounds of formula XXVI wherein R³ represents --NHCH₂ R²⁵ wherein R²⁵represents the hydrogen atom or a straight- or branched-chain alkylgroup containing from 1 to 4 carbon atoms may be prepared by reaction ofa compound of formula XXVI, wherein R³ represents --N═C(OR²⁶)R²⁵ whereinR²⁶ represents a straight- or branched-chain alkyl group containing from1 to 4 carbon atoms, with a reducing agent, preferably sodiumborohydride. The reaction may be effected in an inert organic solvent,ethanol or methanol being preferred, at a temperature from 0° C. to theboiling point of the reaction mixture.

According to process version "dd", which is a further feature of thepresent invention, compounds of formula XXVI, wherein R¹ represents afluorine, chlorine, bromine or iodine atom, may be prepared by thereplacement by known methods of an amino group by a halogen atom, forexample by diazotization of a compound corresponding to formula XXVIIwherein R¹ is replaced by the amino group and the hydrogen atom in the4-position of the pyrazole ring is replaced by the nitro group, usingsodium nitrite in tetrafluoroboric acid and sulphuric acid at atemperature of -10° to +10° C. followed by photolysis in an excess oftetrafluoroboric acid at a temperature of -30° to +30° C. to obtain acompound wherein R¹ represents a fluorine atom, or with an alkylnitrite, preferably tertiary butyl nitrite, in the presence of ahalogenating agent, preferably anhydrous copper chloride, bromoform oriodine respectively, at a temperature from 0° C. to 100° C. to obtain acompound wherein R¹ represents a chlorine, bromine or iodine atom.

According to process version "ee", which is a further feature of thepresent invention compounds of formula XXVI, wherein R³ represents ahalogen atom, may be prepared by diazotization of the correspondingcompound of formula XXVI wherein R³ represents the amino group, in asimilar manner to that hereinbefore described in process version "dd".

Compounds of the formula XXVII, wherein R¹ represents the nitro groupand R³ is as hereinbefore defined but not the unsubstituted amino groupmay be prepared by oxidation of a compound of formula XXXIII, whereinR^(1a) represents the amino group, R^(3a) is as hereinbefore defined forR³ except that R^(3a) does not represent the unsubstituted amino group,and R⁸, R⁶ and R⁴ are as hereinbefore defined, with trifluoroaceticperacid (which is prepared in situ from trifluoroacetic anhydride andhydrogen peroxide (85% w/w)) in dichloromethane at a temperature betweenambient and the boiling point of the solvent.

Compounds of formula XXXIII, wherein R^(1a) represents the amino groupand R⁸, R⁶, R⁴ and R^(3a) are as hereinbefore defined, can be preparedby performing a Curtius rearrangment of the corresponding acid azide byheating in an inert solvent such as toluene at a temperature from 50° to150° C. to give an isocyanate which is then treated with tertiarybutanol at a temperature between 50° and 150° C. to give a carbamatewhich in turn is hydrolyzed using dilute hydrochloric acid in ethanol orusing iodotrimethylsilane in an inert solvent such as acetonitrile at atemperature between ambient and the boiling point of the solvent.

The intermediate acid azide may be prepared from compounds correspondingto formula XXXIII, wherein R^(1a) is replaced by the carboxy group(prepared by hydrolysis of the corresponding ester) with an azidetransfer agent preferably diphenylphosphonylazide in a solvent such asdimethyl formamide in the presence of triethylamine at a temperaturefrom ambient to 100° C.

The intermediate ester is prepared by treating a phenylhydrazine offormula XXXIV with a compound of formula XXXV wherein R²⁷ preferablyrepresents ethyl, by treatment with dilute mineral acid e.g. sulphuricacid, followed by reaction in a lower alkanol solvent, preferablyethanol, at ambient temperature to the boiling point of the solvent.

According to process version "ff", which is a further feature of thepresent invention, compounds of the formula XXVI, wherein R³ representsa hydrogen atom may be prepared by treatment of a compound of formulaXXVI wherein R³ represents the amino group, with an alkyl nitrite,preferably tertiary butyl nitrite, in an inert organic solvent,preferably tetrahydrofuran, at ambient to reflux temperature.

Intermediates of formula XXXVI, wherein R^(1b) represents the cyanogroup or a chlorine or fluorine atom, may be prepared by reaction of anappropriately substituted phenylhydrazine (or acid addition saltthereof) of formula XXXIV with tetracyanoethylene ordichloromethylenemalononitrile or difluoromethylenemalononitrile, in aninert solvent, for example ethanol or acetic acid, at a temperature fromambient to reflux, optionally (or in the case of an acid addition salt)in the presence of a base, i.e. potassium carbonate or triethylamine.

Intermediates corresponding to formula XXVII, wherein R¹ represents afluorine, chlorine, bromine or iodine atom and the hydrogen atom in the4-position of the pyrazole ring is replaced by a group R^(2a) whichrepresents a cyano or formyl group or the group R²⁷ OC(═O), wherein R²⁷represents an alkyl group containing from 1 to 8 carbon atoms,preferably the ethyl group, may be prepared by diazotization of acompound corresponding to formula XXVII wherein R¹ is replaced by theamino group and the hydrogen atom in the 4-position of the pyrazole ringis replaced by a group R^(2a), using sodium nitrite in tetrafluoroboricacid and sulphuric acid at a temperature of -10° to +10° C. followed byphotolysis in an excess of tetrafluoroboric acid at a temperature of-30° to +30° C. to obtain a compound wherein R¹ represents a fluorineatom, or with an alkyl nitrite, preferably tertiary butyl nitrite, inthe presence of a halogenating agent, preferably anhydrous copperchloride, bromoform or iodine respectively, at a temperature from 0° C.to 100° C. to obtain a compound wherein R¹ represents a chlorine,bromine or iodine atom.

Intermediate esters corresponding to formula XXVII, wherein R¹represents a chlorine, bromine or iodine atom, or R¹ represents thefluorine atom, R³ represents the amino group and the hydrogen atom inthe 4-position of the pyrazole ring is replaced by a group R²⁷ OC(═O)--wherein R²⁷ is as hereinbefore defined, may be prepared by diazotizationof a compound of formula XXXVII wherein R²⁷ is as hereinbefore definedin a similar manner to process version "dd", as hereinbefore described

Intermediate diaminoesters of formula XXXVII wherein R²⁷ is ashereinbefore defined may be prepared by reaction of an appropriatelysubstituted phenylhydrazine (or acid addition salt thereof) of formulaXXXIV with an alkali metal salt of an alkyl dicyanoacetate, preferablypotassium ethyl dicyanoacetate, in hydrochloric acid at ambient toreflux temperature. Alkyl dicyanoacetate potassium salts may be preparedby reaction of the appropriate alkyl chloroformate with malononitrile inthe presence of potassium hydroxide in tetrahydrofuran at a temperaturebetween 0° and 100° C.

Intermediate aldehydes corresponding to formula XXVII, wherein R¹represents the cyano group or a chlorine or fluorine atom and thehydrogen atom in the 4-position of the pyrazole ring is replaced by theformyl group, may be prepared by reduction of a compound of formulaXXXVI, wherein R^(1b) is as defined above, with Raney nickel in formicacid, at reflux or with di-isobutylaluminum hydride in an inert solventsuch as tetrahydrofuran at -78° to 0° C.

Intermediates of formula XXVII, wherein R³ represents the hydrogen atom,may be prepared by treatment of the corresponding compound of formulaXXVII, wherein R³ represents the amino group, in a similar manner toprocess version "ff" as hereinbefore described.

Intermediates of formula XXXVIII wherein R¹ represents a halogen atom orthe nitro group may be prepared by reaction of compounds correspondingto formula XXVII, wherein R¹ represents a halogen atom or the nitrogroup, R³ represents the amino group and the hydrogen atom in the4-position of the pyrazole ring is replaced by a formyl or R²⁷ OC(═O)--group, by heating at reflux in a mixture of a mineral acid, e.g.hydrochloric acid, and acetic acid.

Intermediates of formula XXVII, wherein R¹ represents bromide or iodinecan be prepared by refluxing compounds of formula XXVII wherein R¹represents chlorine in a mixture of acetic acid and either hydrobromicor hydroiodic acid respectively

Intermediates of formula XXXVIII wherein R¹ represents the cyano groupmay be prepared by diazotization of the appropriate aniline with asolution of a molar equivalent of sodium nitrite in a mineral acid, e.g.a mixture of concentrated sulphuric acid and acetic acid at atemperature from 0° to 60° C., and then reacting with the compound offormula NCCH₂ CH(CN)COR⁰ wherein R⁰ represents an alkoxy, preferablyethoxy, group in the presence of an inert solvent, e.g. a mixture ofwater and ethanol, buffered, e.g. with excess sodium acetate, and at atemperature from 0° to 50° C.

Intermediates of formula XXXVIII wherein R¹ represents the cyano groupmay also be prepared by reacting the corresponding carboxylic acid witha chlorinating agent, preferably thionyl chloride at ambient to refluxtemperature, followed by reaction of the intermediate acid chloride withammonia to give an intermediate amide which is then dehydrated byheating with a dehydrating reagent, preferably phosphorus oxychloride ata temperature from 50°-250° C.

Intermediate carboxylic acids above may be prepared by hydrolysis of thecorresponding esters preferably using a base such as sodium hydroxideand a solvent such as aqueous alcohol, and at a temperature from 0° C.to the reflux temperature of the reaction mixture.

Compounds of formula XXXIV can be prepared by methods known per se.

The following Examples and Reference Examples illustrate the preparationof compounds of the second embodiment of the invention of formula XXVI:

[Chromatography was effected on a silica column (Merck 0.040-0.063 mm)at a pressure of 6.8Nm⁻² unless otherwise stated.]

EXAMPLE 30 Compounds 102, 103 and 104

Fuming nitric acid (1.7 ml) was added dropwise to a stirred solution of5-acetamido-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole(4.7 g) and acetic anhydride (1 ml) in glacial acetic acid (60 ml).After 1.5 h the reaction mixture was heated to 60° C. and stirred atthis temperature for 5 h. The reaction mixture was cooled, poured intowater (200 ml), basified with saturated potassium carbonate solution (topH 12) and extracted with diethyl ether. The extracts were washed withsaturated sodium bicarbonate solution (2×100 ml), dried and evaporatedto give a brown gum (4.0 g). This was purified by column chromatographyusing dichloromethane as eluent to give5-acetamido-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole(2.9 g) , m.p. 179°-180.5° C., in the form of colorless crystals.

By proceeding in a similar manner but replacing5-acetamido-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole bythe hereinafter indicated substituted pyrazole, there were obtained:

5-Acetamido-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole,m.p. 177°-178.5° C., in the form of colorless crystals, from5-acetamido-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole.

5-Acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole,m.p. 226°-228.5° C., in the form of a cream-colored solid, from5-acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole.

EXAMPLE 31 Compounds 105, 106 and 107

A mixture of5-acetamido-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole(1.0 g), hydrobromic acid (48%; 5 ml) and dioxan (15 ml) was boiledunder reflux for 18 h. The reaction mixture was cooled and evaporated invacuo and the residue treated with water to precipitate a solid whichwas filtered off and dried at 100° C. to give5-amino-3-bromo-1-2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole(0.8 g), m.p. 235°-236° C., in the form of a colorless solid.

By proceeding in a similar manner but replacing5-acetamido-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazoleby the hereinafter indicated substituted pyrazole and replacinghydrobromic acid by 6M hydrochloric acid, there were obtained:

5-Amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole,m.p. 219°-220.5° C., in the form of colorless crystals from5-acetamido-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazoleafter purification by chromatography using dichloromethane as eluantfollowed by recrystallization from dichloromethanehexane.

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole,m.p. 255.5°-256.5° C., in the form of a cream-colored solid, from5-acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazoleafter purification by recrystallization from toluene.

EXAMPLE 32 Compound 108

Tertiary butyl nitrite (6.6 ml) was added at room temperature to asolution of5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole(3.7 g), bromoform (13.3 ml) and acetonitrile (10 ml). The mixture washeated at 50°-60° C. for 4.5 hours and the solvents were evaporated togive an orange oil. This was purified by medium pressure liquidchromatography (eluant hexane/ether 2:1) to give5-bromo-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitropyrazole(3.4 g) as a solid, m.p. 147°-150° C.

REFERENCE EXAMPLE 12

Pyridine (4.0 ml) was added dropwise to a stirred solution of5-amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole (5.0g), acetyl chloride (3.0 g) and dry chloroform (30 ml), causing anexothermic reaction (maximum temperature 60° C.). The reaction mixturewas stirred at laboratory temperature for 2 h and evaporated to dryness.The residue was dissolved in ethanol (25 ml), ammonia solution (d.0.880; 25 ml) was added, and the solution was boiled under reflux for 1h. The cooled reaction mixture was evaporated to dryness, dissolved indichloromethane (100 ml), washed with dilute hydrochloric acid (3×50 ml)and water (50 ml), dried over anhydrous magnesium sulphate, filtered,and evaporated to give5-acetamido-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole(5.3 g), m.p. 180°-187° C., in the form of a pale brown solid.

By proceeding in a similar manner but replacing5-amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole by thehereinafter indicated substituted pyrazole, there were obtained:

5-Acetamido-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole,m.p. 195°-197° C., in the form of a colorless solid after chromatographyusing dichloromethane as eluent from5-amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole.

5-Acetamido-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole,m.p. 200.5°-201.5° C., in the form of an orange solid, from5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole.

REFERENCE EXAMPLE 13

A mixture of5-amino-4-carboethoxy-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole(3.3 g), hydrobromic acid (45%; 30 ml) and acetic acid (50 ml) wasboiled under reflux for 18 h. The mixture was evaporated to low bulk andbasified with sodium hydroxide solution (2M), and the product wasfiltered off, dried (2.9 g) and recrystallized from a mixture of ethanoland water to give5-amino-3-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole (2.5g), m.p. 132.5°-134° C. in the form of a colorless solid.

REFERENCE EXAMPLE 14

Tertiary butyl nitrite (15.0 g) was added dropwise to a stirred mixtureof4-carboethoxy-3,5-diamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole(50.0 g), copper (II) chloride (21.0 g) and acetonitrile (600 ml) over aperiod of 10 min., with the temperature kept at 0° C. by externalcooling. The reaction mixture was stirred at this temperature for 2 hand for a further 2 h at laboratory temperature, evaporated to low bulk,and poured into hydrochloric acid (5M; 1.51). The resultant solution wasextracted with dichloromethane (3×100 ml) and the extracts were washedwith hydrochloric acid (2M; 2×600 ml), dried over magnesium sulphate,filtered and evaporated to give a brown tar. The material was purifiedby dry-column chromatography on a silica gel column withdichloromethane:hexane (4:1) as eluent, followed by medium-pressurechromatography with the same solvents to give5-amino-4-carboethoxy-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole(15.8 g), m.p. 143°-146.5° C., in the form of an orange solid.

REFERENCE EXAMPLE 15

A mixture of5-amino-4-carboethoxy-3-chloro-1-(2,6-dichloro-4-carboethoxy-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole(5.0 g), hydrochloric acid (6M; 75 ml) and acetic acid (75 ml) wasboiled under reflux for 24 h. The mixture was evaporated to low bulk andbasified to pH 12 with sodium hydroxide solution (2M), and the productwas extracted with diethyl ether (3×75 ml). The combined extracts wereevaporated to give a yellow, gummy solid (3.5 g). This was dissolved-ina mixture of hydrochloric acid (6M; 30 ml) and dioxan (60 ml) and boiledunder reflux for 48h. Volatile materials were removed in vacuo and theresidue was purified by chromatography with dichloromethane:hexane (4:1)as eluent to give5-amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole (1.3g), m.p. 128°-129° C. in the form of an off-white solid.

REFERENCE EXAMPLE 16

Ethyl dicyanoacetate potassium salt (35.2 g) was added to a stirredsuspension of 2,6-dichloro-4-trifluoromethylphenylhydrazine (49 g) inhydrochloric acid (0.9M; 220 ml) and the mixture was stirred and boiledunder reflux for 18 h, then cooled to precipitate a solid which wasfiltered off, triturated with diethyl ether (250 ml) and dried to givean off-white solid which was recrystallized from ethyl acetate-hexane togive4-carboethoxy-3,5-diamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole(29.2 g), m.p. 196°-197° C., in the form of an off-white solid.

REFERENCE EXAMPLE 17

Sodium nitrite (8.8 g) was added slowly to stirred concentratedsulphuric acid (90 ml) and the resultant solution, when cool, was addeddropwise, over a period of 20 min., to a solution of2,6-dichloro-4-trifluoromethylaniline (23.0 g) in acetic acid (180 ml)with the temperature kept below 30° C. The mixture was then cooled to 5°C. and added dropwise over 35 min. to a stirred solution of ethyl2,3-dicyanopropanoate (17.1 g), sodium acetate (300 g), water (1.21) andethanol (1.5 ml), with the temperature maintained at 17°-22° C. Themixture was stirred at room temperature for 2.5 h, left overnight,diluted with water (2.01) and extracted with dichloromethane (3×500 ml).The combined extracts were washed three times with dilute sodiumhydroxide solution and once with brine, dried over anhydrous magnesiumsulphate and evaporated in vacuo to give a brown oil (25.2 g). Theresidue was dissolved in a minimum amount of a hot toluene-hexanemixture and treated with charcoal. The solution was filtered and oncooling it gave5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-pyrazole (8.7g), m.p. 141°-142° C., in the form of a pale brown solid.

REFERENCE EXAMPLE 18

A solution of ethyl chloroformate (520 g), malononitrile (330 g) andtetrahydrofuran (500 ml) was added dropwise over 1 h to a stirredsolution of potassium hydroxide (560 g) and water (2.01) at atemperature kept below 40° C. by external ice-cooling. The reactionmixture was stirred at laboratory temperature for 1 h, then cooled to 0°C. to precipitate a solid which was filtered off and dried overphosphorus pentoxide to give ethyl dicyanoacetate potassium salt (334.4g) in the form of an off-white solid.

Compounds of the third embodiment of general formula I conforming toformula XL wherein Y¹ represents the cyano or nitro group or a groupR'SO₂, R'SO or R'S, a straight- or branched-chain alkoxycarbonyl groupcontaining from 2 to 7 carbon atoms, or a straight- or branched-chainalkyl group containing from 1 to 6 carbon atoms which may beunsubstituted or substituted by one or more halogen atoms, Z¹ representsthe unsubstituted amino group or a straight- or branched-chain alkylgroup containing from 1 to 4 carbon atoms, and R²⁸ represents afluorine, chlorine or bromine atom, the cyano group or a straight- orbranched-chain alkyl group containing from 1 to 4 carbon atoms which maybe unsubstituted or substituted by one or more halogen atoms, or acycloalkyl group containing from 3 to 6 carbon atoms, may be prepared bythe process which comprises

(i) the reaction of a compound of the formula XLI, or an acid additionsalt thereof, e.g. the hydrochloride, with (1), when R²⁸ in the compoundof formula XL represents a fluorine, chlorine or bromine atom, anoptionally halogenated straight- or branched-chain alkyl groupcontaining from 1 to 4 carbon atoms or a cycloalkyl group containingfrom 3 to 6 carbon atoms, a compound of the formula XLII, wherein R²⁹represents the cyano group or a straight- or branched-chain alkanoylgroup containing from 2 to 5 carbon atoms and R³⁰ represents a straight-or branched-chain alkoxy group containing from 1 to 4 carbon atoms,preferably ethoxy, the hydroxy group or a fluorine, chlorine or bromineatom, or (2), when R²⁸ in the compound of formula XL represents thecyano group (and Y¹ represents the cyano group and Z¹ represents theunsubstituted amino group), tetracyanoethylene.

The reaction of a compound of formula XLI with a compound of formulaXLII (optionally prepared in situ) or tetracyanoethylene may be effectedin the presence of an inert organic solvent, for example an alkanolcontaining from 1 to 4 carbon atoms, e.g. ethanol, acetic acid,ethoxyethanol or an ether, and at a temperature from ambient temperatureto the reflux temperature of the reaction mixture and optionally in thepresence of an alkali metal, e.g. sodium or potassium, acetate,carbonate or bicarbonate or organic base, e.g. triethylamine. When anacid addition salt of the compound of formula XLI is used, the reactionwith the compound of formula XLII is effected in the presence of analkali metal, e.g. sodium or potassium, acetate, carbonate orbicarbonate.

(ii) Compounds of formula XL wherein Z¹ represents the unsubstitutedamino group may alternatively be prepared directly by reacting acompound of formula Y¹ CH₂ CN with a compound of formula XLI in thepresence of a compound of formula R³¹ C(R⁰)₃ wherein R³¹ represents astraight- or branched-chain alkyl group containing from 1 to 4 carbonatoms which may be unsubstituted or substituted by one or more halogenatoms or a cycloalkyl group containing from 3 to 6 carbon atoms and R⁰represents an alkoxy group which may be straight- or branched-chain andpreferably contains from 1 to 4 carbon atoms, in an inert organicsolvent, preferably ethanol, at a temperature from ambient to reflux.

(iii) Compounds of formula XL wherein Z¹ represents the unsubstitutedamino group and R²⁸ represents the cyano group may be obtained by thereaction of a compound of the formula XLIII with a molar equivalent ofcompound of formula Y¹ CH₂ CN, i.e. malononitrile when Y¹ represents thecyano group, generally in the presence of an ahydrous inert organicsolvent, e.g. ethanol, and a molar equivalent of a base, e.g. sodiumhydride, and at a temperature from 0° to 50° C.

The compounds of formula XL may be prepared by reaction of a compound offormula XLI with a compound of formula XLII or tetracyanoethylene withisolation of an intermediate compound of formula (XLIV) from thereaction mixture. When the reaction of a compound of formula XLI with acompound of formula XLII is effected in acetic acid, in the absence orpresence of an alkali metal, e.g. sodium or potassium, acetate, theintermediate compound of formula XLIV may separate from the reactionmixture, depending upon its solubility in the reaction medium, and may,if desired, be isolated before being cyclized as hereinbefore describedto a compound of formula XL. The cyclization of a compound of formulaXLIV, which constitutes a feature of the invention may be effected inthe presence of an inert organic solvent, for example an alkanolcontaining from 1 to 4 carbon atoms, e.g. ethanol, acetic acid orethoxyethanol, at a temperature of from ambient temperature up to thereflux temperature of the reaction mixture, and optionally in thepresence of sodium ethoxide when the solvent is ethanol.

It will be appreciated that in the preparation of compounds of generalformula I corresponding to the third embodiment of the invention thefollowing subsidiary processes or adaptations thereof may be performedin an appropriate combination to achieve the compound sought.

Compounds of general formula I which conform to formula XLV wherein R"represents an R³³ C(═O)-- group, wherein R³³ represents a straight- orbranched-chain alkyl or alkoxy group containing from 1 to 6 carbonatoms, or a cycloalkyl group containing from 3 to 6 carbon atoms and R'"represents a hydrogen atom or an R³³ C(═O)-- group which is identical tothe group R³³ C(═O)-- represented by R" or --NR³² R'" represents acyclic imide as hereinbefore defined, may be prepared by the reaction ofa compound of general formula I wherein R³ represents the unsubstitutedamino group, or an alkali metal salt thereof, with a compound of theformula XLVI:

    R.sup.33 COX.sup.9                                         XLVI

wherein X⁹ represents a chlorine or bromine atom, or with a compound ofthe formula XLVII:

    (R.sup.33 CO).sub.2 O                                      XLVII

or with a dicarboxylic acid derivative. The reaction may be conducted inthe absence or presence of an inert organic solvent, for exampleacetonitrile, tetrahydrofuran, a ketone, e.g. acetene, an aromatichydrocarbon, e.g. benzene or toluene, chloroform, dichloromethane ordimethylformamide, and optionally in the presence of an acid-bindingagent, for example pyridine, triethylamine or an alkali metal, e.g.sodium or potassium, carbonate or bicarbonate, at a temperature from 0°C. to the reflux temperature of the reaction medium, to give a compoundof formula XLV wherein R" represents an R³³ C(═O)-- group wherein R³³ isas hereinbefore defined and R'" represents a hydrogen atom or an R³³C(═O)-- group, depending upon the reaction conditions chosen and/or theuse of an excess of the compound of formula XLVI or XLVII.

Compounds of formula XLV wherein R" represents a formyl group and R'"represents a hydrogen atom may be prepared by reaction of a compound ofgeneral formula I of the third embodiment of the invention, wherein R³represents the unsubstituted amino group with formic acid. The reactionmay be conducted in an inert organic solvent, for example a ketone, e.g.methylisobutylketone, or an aromatic hydrocarbon, e.g. benzene ortoluene, at the reflux temperature of the reaction mixture.

Compounds of formula XLV wherein R" represents a formyl group and R'"represents a hydrogen atom or a formyl group, may be prepared by thereaction of a compound of general formula I, wherein R³ represents theunsubstituted amino group with formylacetic anhydride. Formylaceticanhydride may be prepared from formic acid and acetic anhydride and thereaction with the compound of general formula I may be conducted in theabsence or prsence of an inert organic solvent, for example a ketone,e.g. acetone, or an aromatic hydrocarbon, e.g. benzene or toluene, andoptionally in the presence of an acid-binding agent, for examplepyridine, triethylamine or an akali metal, e.g. sodium or potassium,carbonate or bicarbonate, at a temperature from 0° C. to the refluxtemperature of the reaction mixture, to give a compound of formula XLVwherein R" represents a formyl group and R'" represents a hydrogen atomor a formyl group, depending upon the reaction conditions chosen and/orthe use of an excess of formylacetic anhydride.

Compounds of formula XLV wherein R" represents a formyl group or a groupR³³ C(═O)-- and R'" represents a hydrogen atom may be prepared by theselective removal by hydrolysis of an R³³ C(═O)-- group or a formylgroup from a compound of formula XLV wherein R" and R'" both represent aR³³ C(═O)-- group or a formyl group. Hydrolysis is effected under mildconditions, for example by treatment with an aqueous-ethanolic solutionor suspension of an alkali metal, e.g. sodium or potassium, bicarbonate,or with aqueous ammonia.

Compounds of formula XLV wherein R" represents a straight- orbranched-chain alkoxycarbonyl group containing from 2 to 7 carbon atomswhich is unsubstituted or substituted by one or more halogen atoms, andR'" represents a hydrogen atom may be prepared by the reaction of acompound of the formula XLVIII, wherein R³⁵ represents an alkoxycarbonylgroup R³⁶ C(═O)--, wherein R³⁶ represents a straight- or branched-chainalkoxy group containing from 1 to 6 carbon atoms (which is unsubstitutedor substituted by one or more halogen atoms) or a phenoxy group, with acompound of the formula XLIX:

    R.sup.36 H                                                 XLIX

to replace a first group represented by the symbol R³⁵ by a hydrogenatom, and to replace the second group represented by the symbol R³⁵ byan alkoxycarbonyl group when R³⁵ represents a phenoxycarbonyl group, or,if desired, to replace the second group represented by the symbol R³⁵ byanother alkoxycarbonyl group when R³⁵ in formula XLVIII represents analkoxycarbonyl group. As will be apparent to those skilled in the art,the desired compound of formula XLV is obtained by selection of theappropriate compounds of formulae XLVIII and XLIX. The reaction may beeffected in water or an inert aqueous-organic or organic solvent, forexample an alkanol containing 1 to 4 carbon atoms, e.g. ethanol, or anaromatic hydrocarbon, e.g. benzene or toluene, or which is preferably anexcess of the compound of formula XLIX, at a temperature from ambienttemperature to the reflux temperature of the reaction mixture and, ifnecessary, at elevated pressure, and optionally in the presence of abase, for example an alkali metal alkoxide, e.g. of the compound offormula XLIX.

Compounds of formula XLV wherein R" and R'", which may be the same ordifferent, each represents a formyl group or a R³³ C(═O)-- group, may beprepared by the reaction of an alkali metal, e.g. sodium or potassium,derivative of a compound of formula XLV wherein R" represents a groupR³³ C(═O)-- as hereinbefore defined, or a formyl group, and R'"represents a hydrogen atom with formic acid, formylacetic arthydride ora compound of formula XLVI. Reaction may be effected in an inert aproticsolvent, e.g. dimethylformamide, at a temperature from laboratorytemperature to the reflux temperature of the reaction mixture.

Alkali metal derivatives of compounds of general formula I (wherein R³represents the unsubstituted amino group) or formula XLV wherein R"represents a group R³³ C(═O)-- and R'" represents a hydrogen atom may beprepared in situ by reaction with an alkali metal, e.g. sodium orpotassium, hydride, in an inert aprotic solvent, e.g. dimethylformamide,at a temperature from laboratory temperature to the reflux temperatureof the reaction mixture.

Compounds of formula XLVIII wherein R³⁵ represents a group R³⁶ C(═O)--,may be prepared as hereinbefore described. Compounds of formula XLVIIIwherein R³⁵ represents a phenoxycarbonyl group may be prepared by thereaction of a compound of general formula I (wherein R³ represents theunsubstituted amino group), with a compound of the formula XLVIA:

    R.sup.37 COX.sup.9                                         XLVIA

wherein R³⁷ represents a phenoxy group, or with a compound of theformula XLVIIA:

    (R.sup.37 CO).sub.2 O                                      XLVIIA

using the reaction conditions hereinbefore described for the reaction ofa compound of general formula I with a compound of formula XLVI orXLVII.

Compounds of formula XLV wherein R" represents a group R³⁸ whichrepresents a straight- or branched-chain alkyl group containing from 1to 6 carbon atoms (which may be unsubstituted or substituted byalkoxycarbonyl groups containing from 2 to 5 carbon atoms) or acycloalkyl group containing from 3 to 6 carbon atoms, and R'" representsa hydrogen atom may be prepared by the removal of the group R³³ C(═O)--of a compound of the formula XLV, wherein R¹ represents a group R³⁸ andR'" represents a group R³³ C(═O)--. Removal of the group R³³ C(═O)-- maybe effected by selective hydrolysis under mild conditions, for exampleby treatment with an alkali metal, e.g. sodium or potassium, hydroxidein water or an inert organic or aqueous-organic solvent, for example alower alkanol, e.g. methanol, or a mixture of water and lower alkanol,at a temperature from laboratory temperature up to the refluxtemperature of the reaction mixture.

Compounds of the formula XLV, wherein R" represents a group R³⁸ and R'"represents a group R³³ C(═O), may be prepared by reaction of a compoundof formula XLV wherein R" represents a hydrogen atom, or an alkalimetal, e.g., sodium or potassium, derivative thereof, with a compound ofthe formula L:

    R.sup.38 X.sup.10                                          L

wherein X¹⁰ represents a chlorine, bromine or iodine atom. Reaction maybe effected in an inert organic solvent, e.g. dichloromethane,tetrahydrofuran, or dimethylformamide, at a temperature from laboratorytemperature up to the reflux temperature of the reaction mixture and,when a compound of formula XLV is used, in the presence of a base, e.g.Triton B; or by reaction of a compound of formula XLV wherein R"represents the hydrogen atom and R" represents a group R³⁸ with acompound of formula XLVI or XLVII.

Compounds of general formula I wherein R³ represents an N-(alkyl orcycloalkyl)-N-formylamino group as hereinbefore described may beprepared in a similar manner to the process above using, whereappropriate, formylacetic anhydride instead of a compound of formulaXLVI or XLVII.

Compounds of formula XLV wherein one of R" and R'" or both of R" and R'"represent a straight- or branched-chain alkyl group containing from 1 to6 carbon atoms or cycloalkyl group containing from 3 to 6 carbon atoms,groups represented by R" and R'" being identical, may be prepared byreaction of a compound of general formula I, wherein R³ represents theunsubstituted amino group, or an alkali metal, e.g. sodium or potassium,derivative thereof, with a compound of formula L, in the absence orpresence of an inert organic solvent, for example an aromatichydrocarbon, e.g. benzene or toluene, chloroform, dichloromethane,tetrahydrofuran or dimethylformamide, and optionally in the presence ofan acid-binding agent, for example pyridine, triethylamine or an alkalimetal, e.g. sodium or potassium, bicarbonate, at a temperature from 0°C. up to the reflux temperature of the reaction mixture.

Alkali metal derivatives of compounds of formulae XLV (wherein R"represents a hydrogen atom) and I (wherein R³ represents theunsubstituted amino group) may be prepared in situ by the reaction ofthe compounds, with an alkali metal, e.g. sodium or potassium, hydride,at a temperature from laboratory temperature to the reflux temperatureof the reaction mixture.

Compounds of general formula I wherein R³ represents a straight- orbranched-chain alkoxymethyleneamino group containing from 2 to 5 carbonatoms which may be unsubstituted or substituted on methylene by astraight- or branched-chain alkyl group containing from I to 4 carbonatoms may be prepared by the reaction of a compound of general formula I(wherein R³ represents the unsubstituted amino group) with atrisalkoxyalkane in the presence of an acidic catalyst, e.g.p-toluenesulphonic acid, at a temperature from ambient temperature tothe reflux temperature of the reaction mixture.

Compounds of general formula I, wherein R³ represents a straight- orbranched-chain alkylsulphenylamino group containing from 1 to 4 carbonatoms, may be prepared by the reaction of compounds of general formula I(wherein R³ represents the unsubstituted amino group) with analkanesulphenyl chloride in the presence of a base, e.g. sodium hydride,and optionally in the presence of a crown ether catalyst, e.g.15-crown-5.

The reaction may be performed in a solvent, e.g. tetrahydrofuran, at atemperature from 0° C. to the reflux temperature of the reactionmixture.

Compounds of general formula I wherein R³ represents --NHCH₂ R³⁹ whereinR³⁹ represents the hydrogen atom or a straight- or branched-chain alkylgroup containing from 1 to 4 carbon atoms may be prepared by reaction ofa compound of general formula I wherein R³ represents --N═C(OR⁴⁰)R³⁹wherein R⁴⁰ represents a straight- or branched-chain alkyl groupcontaining from 1 to 4 carbon atoms with a reducing agent, preferablysodium borohydride. The reaction may be effected in an inert organicsolvent, ethanol or methanol being preferred, at a temperature from 0°C. to the reflux temperature of the reaction mixture.

Compounds of general formula I wherein R² represents --C(═O)NH₂ may beprepared by partial hydrolysis of a compound of general formula Iwherein R² represents --CN preferably with sulphuric acid at atemperature from ambient temperature to 100° C.

Compounds of general formula I wherein R² represents the chlorine,bromine or iodine atom may be prepared by reaction of a compound offormula LI with a halogenating agent, preferably N-halosuccinimide in aninert solvent, preferably carbon tetrachloride, at a temperature fromambient temperature to the reflux temperature of the reaction mixture.

Compounds of general formula I wherein R³ represents the chlorine,bromine or iodine atom may be prepared by diazotization of a compound ofgeneral formula I wherein R³ represents --NH₂ with an alkyl nitrite,preferably tert-butyl nitrite, in the presence of a halogenating agentpreferably bromoform, iodine or anhydrous copper chloride at atemperature from 0° C. to 100° C.

Compounds of general formula I wherein R² represents the nitro group maybe prepared by reacting a compound of formula LI with a nitrating agent,preferably nitric acid optionally in the presence of sulphuric acid ornitric acid in a solvent such as acetic acid or acetic anhydride at atemperature from 0° C. to 100° C.

Compounds of general formula I wherein R² represents --SO₂ NR⁴¹ R⁴²wherein R⁴¹ and R⁴², which may be the same or different, each representthe hydrogen atom or a straight- or branched-chain alkyl groupcontaining from 1 to 6 carbon atoms may be prepared by reacting acompound of formula LIV with an amine of the formula R⁴¹ R⁴² NH in asolvent such as toluene or water at a temperature from 0° C. to thereflux temperature of the reaction mixture.

Compounds of general formula I wherein R² represents --CONR⁴¹ R⁴² may beprepared by reacting a compound of formula LV wherein X^(la) representsa chlorine or bromine atom or activated ester moiety, e.g.4-nitrophenoxy group, especially the chlorine atom, with an amine of theformula R⁴¹ R⁴² NH, in a solvent such as toluene or water, at atemperature from 0° C. to the reflux temperature of the reactionmixture.

Intermediates of formula LI may be prepared by decarboxylation of acompound of formula LVI, performed by heating at a temperature from 100°C. to 250° C., optionally in the presence of an inert organic solvent,particularly N,N-dimethylaniline.

Intermediates of formula LI wherein R³ is the unsubstituted amino groupand R¹ represents a straight- or branched-chain alkyl group containingfrom 1 to 4 carbon atoms which may be unsubstituted or substituted byone or more halogen atoms may also be prepared by reaction of anappropriate β-ketonitrile or derivative thereof, e.g. the imine with anarylhydrazine in an inert organic solvent such as ethanol optionally inthe presence of an acidic or basic catalyst at a temperature fromambient to 100° C.

Alternatively, intermediates of formula LI may be prepared directly fromesters of compounds of formula LVI by heating in an inert organicsolvent preferably acetic acid at a temperature from 50° C. to reflux,in the presence of a strong acid preferably hydrobromic acid.

Intermediates of formula LVI may be prepared by hydrolysis of esters ofgeneral formula I wherein R² represents --COOR⁴³ wherein R⁴³ representsa straight- or branched-chain alkyl group containing from 1 to 6 carbonatoms, preferably with an alkali metal hydroxide in a solvent such as anaqueous alcohol at a temperature from 0° C. to the reflux temperature ofthe reaction mixture.

Intermediates of formula LIV may be prepared by reacting a compound offormula LI with chlorosulphonic acid at a temperature from 0° C. to 150°C.

Intermediates of formula LV are prepared by reacting a compound offormula LVI with a chlorinating or brominating agent or e.g.4-nitrophenol (preferably thionyl chloride) at a temperature fromambient temperature to the reflux temperature of the reaction mixture.

Compounds of general formula I wherein R² represents --C(═O)R⁴³ whereinR⁴³ represents a straight or branched-chain alkyl group containing fromI to 6 carbon atoms may be prepared by the reaction of a compound offormula LI with an acylating agent such as R⁴³ COCl in the presence of acatalyst such as aluminum chloride and in an inert organic solvent suchas 1,1,2,2-tetrachloroethane and at a temperature from 0° C. to thereflux temperature of the reaction mixture.

When R³ is an amino group it may also be acylated and subsequenthydrolysis using an acid such as hydrochloric or hydrobromic acid in asolvent such as dioxan or acetic acid may be necessary.

Compounds of general formula I wherein R² represents --C(═O)R⁴³ may alsobe prepared by the reaztion of nitriles of the general formula I whereinR² represents --CN with an organometallic reagent such as a compound offormula R⁴³ MgX¹⁰ in an inert organic solvent such as diethyl ether ortetrahydrofuran, at a temperature from 0° C. to reflux.

Compounds of formula LVII may be prepared by the reaction of a compoundof formula I wherein R² represents the thiocyanato group with anorganometallic reagent such as a compound of formula R'MgX¹⁰ in an inertorganic solvent such as diethyl ether or tetrahydrofuran, and at atemperature from ambient temperature to the reflux temperature of thereaction mixture.

Compounds of formula LVII wherein R'S is other than a 1-alkenylthiogroup may also be prepared by reacting a compound of general formula Iwherein R² represents the thiocyanato group with a base, preferablysodium hydroxide, or a reducing agent, preferably sodium borohydride, inthe presence of a reagent of formula R^(a) X¹⁰ wherein R^(a) is ashereinbefore defined for R' with the exclusion of 1-alkenyl groups, forexample methyl iodide in an inert organic or aqueous-organic solventsuch as an alcohol, e.g. ethanol or a mixture of an alcohol and water,the reaction being performed at a temperature from ambient to reflux.

Alternatively, compounds of formula LVII wherein R'S is other than a1-alkenylthio group may be prepared by reductive alkylation ofdisulphides of formula LVIII employing a reducing agent preferablysodium dithionite or sodium borohydride, in the presence of a base,preferably sodium hydroxide or sodium carbonate, and of a reagent offormula R^(a) X¹⁰ such as methyl iodide in an inert organic oraqueous-organic solvent such as an alcohol, e.g. ethanol or a mixture ofan alcohol and water, at a temperature from ambient to reflux.

Alternatively, compounds of formula LVII may be prepared from a halideof general formula I wherein R² represents a bromine or iodine atom bymetal exchange using a strong base, preferably butyl lithium, andsubsequent addition of the appropriate disulphide of formulaR'--S--S--R' in an inert organic solvent such as tetrahydrofuran, andthe reaction is performed at a temperature from -78° C. to ambient.

Alternatively, compounds of formula LVII wherein R'S represents astraight- or branched-chain alkylthio group containing from 1 to 6carbon atoms which may be unsubstituted or substituted by one or morehalogen atoms may be prepared by reacting a compound of formula LI withan alkanesulphenyl halide (which may be optionally substituted by one ormore halogen atoms) in an inert organic solvent, preferably chloroform,in the presence of a base such as pyridine, and at temperatures from 0°C. to reflux.

Compounds of formula LVII wherein R'S represents a methylthio groupwhich is substituted by three halogen atoms which may be the same ordifferent may also be prepared by the reaction of a compound of generalformula I wherein R² represents the thiocyanato group with a source ofhalogenocarbene, such as chloroform and sodium hydroxide, preferablywith phase transfer catalysis using for example benzyltriethylammoniumchloride or tetrabutyl-ammonium chloride.

Compounds of formula LVII wherein R'S represents a straight- orbranched-chain alkylthio group containing from 1 to 6 carbon atoms whichis substituted by one or more fluorine atoms may also be prepared by ahalogen exchange reaction of a compound of formula LVII wherein R'Srepresents a straight- or branched-chain alkylthio group containing from1 to 6 carbon atoms which is substituted by one or more chlorine atomswith a fluorinating agent such as a mixture of antimony trifluoride andantimony pentachloride, KF or CsF in an aprotic solvent such assulfolane at a temperature from 50° C. to reflux.

Compounds of general formula I wherein R² represents the thiocyanatogroup may be prepared by the reaction of a compound of formula LI with athiocyanating agent such as alkali metal or ammonium salts of thiocyanicacid (e.g. NaSCN) and bromine in an inert organic solvent such asmethanol, and at a temperature from 0° C. to 100° C.

Intermediates of formula LVIII may be prepared by hydrolysis ofthiocyanates of general formula I wherein R² represents the thiocyanatogroup, preferably using hydrochloric acid in the presence of ethanol ata temperature from ambient to reflux temperature; they may also beprepared by reduction of the thiocyanates by sodium borohydride in analcohol preferably ethanol at a temperature from ambient to reflux.

Compounds of general formula I wherein R² represents a group R'SO may beprepared by the oxidation of compounds of formula LVII by an oxidizingreagent preferably 3-chloroperbenzoic acid in an inert organic solventsuch as dichloromethane or by hydrogen peroxide in acetic acid at atemperature from 0° C. to the reflux temperature of the reaction medium.

Compounds of general formula I wherein R² represents a group R'SO₂ mayalso be prepared by the above process, by employing an excess of theoxidizing agent.

Compounds of general formula I wherein R² represents a group R'SO₂wherein R' represents a straight- or branched-chain alkyl groupcontaining from 1 to 6 carbon atoms which is substituted by one or morefluorine atoms may also be prepared by a halogen exchange reaction of acompound of general formula I wherein R² represents a group R'SO₂wherein R' represents a straight- or branched-chain alkyl groupcontaining from 1 to 6 carbon atoms which is substituted by one or morechlorine atoms with a fluorinating agent such as a mixture of antimonytrifluoride and antimony pentachloride, KF or CsF at a temperature from50° C. to 200° C.

Compounds of general formula I wherein R² represents a group R'SO₂ mayalso be prepared by reaction of a compound of general formula LI withthe appropriate sulphonic anhydride of general formula (R'SO₂)₂ O forexample trifluoromethanesulphonic or methanesulphonic anhydride and inthe presence of aluminum chloride as catalyst, and employing an inertorganic solvent such as 1,1,2,2-tetrachloroethane at a temperature fromambient to 150° C.

Compounds of general formula I wherein R³ represents a straight- orbranched-chain alkyl group containing from 1 to 4 carbon atoms, thecarboxy group, a group R⁴⁴ S wherein R⁴⁴ represents a straight- orbranched-chain alkyl group containing from 1 to 6 carbon atoms which maybe unsubstituted or substituted by one or more halogen atoms or R³represents a trialkylsilyl group containing from 1 to 6 carbon atoms ineach alkyl group which may be the same or different may be prepared bythe reaction of a compound of general formula I wherein R³ represents ahydrogen, bromine or iodine atom with a lithiating agent preferablylithium diisopropylamide or n-butyl lithium, and reaction with theappropriate substrate from alkyl halide, carbon dioxide,dialkylsulphides or trialkylsilyl halides respectively at a temperaturefrom -78° C. to ambient temperature, and in an inert solvent, preferablytetrahydrofuran.

Compounds of general formula I wherein R³ represents a hydrogen atom maybe prepared by diazotization of an amine of general formula I wherein R³represents the unsubstituted amino group using an alkyl nitrite,preferably tert-butyl nitrite, in an inert solvent preferablytetrahydrofuran, at a temperature from ambient temperaure to the refluxtemperature of the reaction mixture.

Compounds of general formula I wherein R³ represents a group R⁴⁴ SO maybe prepared by the reaction of a compound of general formula I wherein Zrepresents a group R⁴⁴ S with an oxidizing agent, preferably3-chloroperbenzoic acid in a solvent such as dichloromethane, or byhydrogen peroxide in acetic acid at a temperature from 0° C. to thereflux temperature of the reaction mixture.

Compounds of general formula I wherein R³ represents a group R⁴⁴ SO₂ mayalso be prepared by the above process, by employing an excess of theoxidizing agent.

Compounds of general formula I wherein R³ represents the fluorine atomor the cyano group may be prepared by the reaction of a halide offormula I wherein R³ represents the chlorine or bromine atom with analkali metal fluoride, preferably cesium fluoride, or with an alkalimetal cyanide preferably KCN, under anhydrous conditions in an inertsolvent, preferably sulfolane, and at a temperature from ambienttemperature to 150° C.

Compounds of general formula I wherein R³ represents the nitro group maybe prepared by oxidation of amines of general formula I wherein R³represents the unsubstituted amino group with an oxidant, preferablytrifluoroperacetic acid or m-chloroperbenzoic acid and in an inertorganic solvent preferably dichloromethane at a temperature from 0° C.to reflux.

Compounds of general formula I wherein R³ represents the cyano group maybe prepared by dehydration of the corresponding amide preferably byheating with phosphorous pentoxide at a temperature from 50° C. to 250°C.

The amides may be prepared (i) by reacting a carboxylic acid of generalformula I wherein R³ represents a carboxy group with a chlorinatingagent preferably thionyl chloride, and (ii) reacting the resultant acidchloride of formula LIX with ammonia:

(i) the reaction with a chlorinating agent preferably thionyl chlorideis generally conducted at a temperature from ambient temperature to thereflux temperature of the reaction mixture;

(ii) the reaction with ammonia is generally conducted in a solvent whichmay be inert, preferably toluene, or in the presence of water, and at atemperature from 0° C. to 100° C.

Compounds of general formula I wherein R² represents a group R'SO₂ isother than a 1-alkenylsulphonyl group may be prepared alternatively byreaction of sulphinate metal (e.g. sodium) salts with a reagent offormula R^(a) X¹⁰ or preferably a sulphate of formula (R^(a))₂ SO₄, in asolvent such as water and in the presence of sodium bicarbonate at atemperature from 0° C. to 100° C.

The intermediate sulphinate sodium salts may be prepared by reaction ofsulphonyl chlorides of formula LIV with sodium sulphite in the presenceof sodium bicarbonate and water as solvent, at a temperature from 50° C.to reflux.

Intermediates of formula LIV may also be prepared from the thiocyanatesof general formula I wherein R² represents a thiocyanato group bychlorination using chlorine in a solvent, preferably water, at atemperature from ambient to reflux.

Compounds of general formula I wherein one of the substituents R⁴ -R⁸represents a haloalkylsulphinyl group may be prepared by oxidation of ahaloalkylthio derivative of general formula I, preferably withm-chloroperbenzoic and in an inert organic solvent preferablydichloromethane, at a temperature from 0° C. to reflux.

Compounds of general formula I wherein one of the substituents R⁴ -R⁸represents a haloalkylsulphonyl group may be prepared in a similarmanner, by employing two molar equivalents of oxidant.

Compounds of general formula I wherein R² represents the fluorine atommay be prepared by diazotization of corresponding amines using sodiumnitrite in tetrafluoroboric acid and sulphuric acid at a temperaturefrom -10° C. to +10° C., followed by photolysis in the presence ofexcess sodium tetrafluoroboric acid at a temperature from -30° C. toambient.

Intermediate amines above may be prepared by reduction of nitrocompounds of general formula I wherein R² represents a nitro group,preferably with zinc in ethanol at a temperature from ambient to reflux.

Compounds of general formula I wherein R² represents the methyl groupmay be prepared by reduction of an acid of general formula LVI using areducing agent, preferably borane-tetrahydrofuran complex in a solventpreferably tetrahydrofuran at a temperature from -30° C. to reflux.

Compounds of general formula I wherein R³ represents atrialkylsilylmethyl group as hereinbefore defined may be prepared by thereaction of a compound of general formula I wherein R³ represents themethyl group with a lithiating agent preferably lithium diisopropylamideor n-butyl lithium, and reaction with a trialkylsilyl halide at atemperature from -78° C. to ambient, and in an inert organic solventpreferably tetrahydrofuran, optionally in an inert atmosphere.

The following processes optionally followed by the subsidiary processeshereinbefore described permit the preparation of the remaining compoundsof general formula I not described above, as well as some whosepreparation is described above.

Compounds of general formula I wherein R¹ represents a chlorine, bromineor iodine atom and R³ represents the unsubstituted amino group, may beprepared by the diazotization of the (diamino) compounds of generalformula I in which R³ represents and R¹ is replaced by amino, using amolar equivalent of sodium nitrite in a mineral acid, for example amixture of concentrated sulphuric acid and acetic acid, at a temperaturefrom 0° to 60° C., and by subsequent reaction with the appropriatecopper salt and appropriate mineral acid or with an aqueous solution ofpotassium iodide (when R¹ represents an iodine atom) at a temperaturefrom 0° to 100° C.

The diamino compounds above wherein R² represents the cyano group may beprepared by the reaction of potassium cyanoform KC(CN)₃ with aphenylhydrazine of formula XLI in the presence of hydrochloric acid, ata temperature from 50° C. to the reflux temperature of the reactionmixture.

Compounds of general formula I wherein R¹ represents the fluoromethylgroup may be prepared by reacting a compound of formula LII with afluorinating agent, preferably diethylaminosulphur trifluoride, in aninert organic solvent, preferably dichloromethane, at a temperature from-78° C. to the reflux temperature of the reaction mixture.

Intermediates of formula LII may be prepared by reduction of compoundsof formula LX preferably with lithium borohydride in an inert organicsolvent, e.g. tetrahydrofuran at a temperature from 0° C. to the refluxtemperature of the reaction mixture.

Intermediates of formulae LX (wherein R⁴⁵ represents an alkyl group) andLXI wherein R³ represents the unsubstituted amino group may be obtainedby the reaction of a compound of the formula LIII (wherein R° representsan alkoxy group) with a molar equivalent of compound of formula Y¹ CH₂CN, i.e. malononitrile when Y¹ represents the cyano group, in thepresence of an anhydrous solvent, e.g. ethanol, and a molar equivalentof a base, e.g. sodium hydride, and at a temperature from 0° to 50° C.followed, if desired, by hydrolysis of the esters of formula LX with anaqueous base, e.g. sodium hydroxide, with a co-solvent, e.g. ethanol, ata temperature from 0° C. to the reflux temperature of the reactionmixture.

Intermediates of formulae XLIII and LIII may be prepared by chlorinationof the appropriate unsubstituted compound using chlorine or otherchlorinating agent.

Intermediates of formulae XLIII and LIII may be prepared bydiazotization of the appropriate aniline with a solution of a molarequivalent of sodium nitrite in a mineral acid, e.g. a mixture ofconcentrated sulphuric acid and acetic acid at a temperature from 0° to60° C., and then reacting with the compound of formula CH₃ COCH(Cl)CN ora compound of formula CH₃ COCH(Cl)COR° wherein R° represents an alkoxygroup in the presence of an inert solvent, e.g. a mixture of water andethanol, buffered, e.g. with excess sodium acetate, and at a temperaturefrom 0° to 50° C.

Compounds of general formula I wherein R¹ represents the nitro group maybe prepared by oxidation of the corresponding amine with an oxidant,preferably trifluoroperacetic acid or m-chloro-perbenzoic acid in aninert organic solvent preferably dichloromethane at a temperature from0° C. to reflux. By employing known protecting agents in this processcompounds of general formula I wherein R³ represents the amino group maybe prepared.

Compounds of general formula I wherein R¹ represents the fluorine atommay be prepared by the diazotization of the corresponding amine ofgeneral formula I in which R¹ is replaced by --NH₂ using for example asolution of sodium nitrite in a mineral acid, for example sulphuric acidand in the presence of fluoroboric acid or its sodium salt andsubsequent thermolysis or photolysis of the diazonium fluoroboratederivative by methods known per se.

Amine intermediates above wherein R³ represents the hydrogen atom may beprepared by performing a Curtius rearrangement of the corresponding acidazide by heating in an inert organic solvent such as toluene at atemperature from 50° to 150° C. to give an isocyanate which is thenreacted with for example tert.-butanol to give a carbamate, which inturn is hydrolyzed using dilute acid preferably hydrochloric acid inethanol at a temperature from ambient to reflux.

Intermediate acid azides may be prepared by reaction of a carboxylicacid of formula LXI wherein R³ represents the hydrogen atom with achlorinating agent, preferably thionyl chloride at temperatures fromambient to reflux, followed by reaction of the intermediate acidchloride with sodium azide in a polar solvent, preferably acetone andwater at a temperature from 0° C. to ambient.

Compounds of general formula I wherein R¹ represents the cyano group mayalso be prepared by reacting a carboxylic acid of formula LXI with achlorinating agent, preferably thionyl chloride at ambient to refluxtemperature, followed by reaction of the intermediate acid chloride withammonia to give an intermediate amide which is then dehydrated byheating with a dehydrating reagent, preferably phosphorus pentoxide at atemperature from 50°-250° C.

Intermediates of formula LXI may be prepared by hydrolysis of thecorresponding esters of formula LX preferably using a base such assodium hydroxide and a solvent such as aqueous alcohol, and at atemperature from 0° C. to the reflux temperature of the reactionmixture.

Compounds of general formula I wherein R² represents a 1,1-difluoroalkylgroup which may be substituted by one or more additional halogen atomsmay be prepared by the reaction of a compound of general formula Iwherein R² represents a straight- or branched-chain alkanoyl groupcontaining from 2 to 6 carbon atoms or the corresponding compound inwhich R² is replaced by the formyl group or a straight- orbranched-chain alkanoyl group containing from 2 to 6 carbon atoms whichis substituted by one or more halogen atoms with a fluorinating agent,preferably diethylaminosulphur trifluoride or sulphur tetrafluoride inan inert organic solvent, preferably dichloromethane, at a temperaturefrom -78° C. to ambient.

Compounds of general formula I wherein R² represents the trifluoromethylgroup or a trifluoromethyl alkyl group containing from 2 to 6 carbonatoms which may be substituted by one or more additional halogen atomsmay be prepared by the reaction of a fluorinating agent, e.g. sulphurtetrafluoride, with an acid of formula LVI or the correspondingcarboxyalkyl compound (it being understood that the carboxy group may beattached to any position of the alkyl moiety) at a temperature fromambient to 150° C.

Salts with pesticidally-acceptable bases of compounds of general formulaI wherein R³ represents the carboxy group may be prepared from thecorresponding compounds of general formula I by methods known per se,for example by reacting stoichiometric quantities of the compound ofgeneral formula I and the appropriate base, for example an alkali metalhydroxide, carbonate or bicarbonate, an alkaline earth metal hydroxideor carbonate, ammonia or an amine (e.g. diethanolamine, triethanolamine,octylamine, morpholine or dioctylamine), in a suitable solvent. Thesalts may, if necessary, be purified by recrystallization from one, twoor more suitable solvents.

Compounds of the third embodiment of the invention according to generalformula I not hitherto disclosed or described in the chemicalliterature, together with their processes of preparation form furtherfeatures of the present invention.

The present invention accordingly provides the compounds of generalformula I, wherein the various symbols are as hereinbefore defined forthe third embodiment of the invention, and salt thereof, with theexclusion of the compounds wherein: R¹ and R³ both represent methyl, R²represents thiocyanato and R⁴ -R⁸ represent 2-, 3- or 4-nitro, 4-methyl,4-chloro or 2,4-dinitro substitution; R¹ represents methyl, R²represents cyano, R³ represents unsubstituted amino and R⁴ -R⁸ represent4-chloro, 2,4-dichloro, 3,4-dichloro, 3-chloro-4-methyl or2-methyl-4-chloro substitution; R¹ represents methyl, R² representscyano or CONH₂, R³ represents unsubstituted amino and R⁴ -R⁸ represent3- or 4-fluoro substitution; R¹ represents ethyl, R² represents cyano orCONH₂, R³ represents unsubstituted amino and R⁴ -R⁸ represent 3- or4-chloro, 2-, 3- or 4-fluoro or methyl, 3-bromo or 3-nitro substitution;R¹ represents propyl, R² represents cyano or CONH₂, R³ representsunsubstituted amino and R⁴ -R⁸ represent 3-fluoro substitution; R¹represents methyl, R² represents sulphamoyl, R³ represents chloro and R⁴-R⁸ represent 4-chloro substitution; R¹ represents methyl, R² representsnitro, and R³ represents chloro or R¹ represents chloro, R² representsnitro, and R³ represents methyl and R⁴ -R⁸ represent 4-nitro; and R¹represents nitro, R² represents cyano or CONH₂, R³ represents hydrogenand R⁴ -R⁸ represent 4-nitro substitution.

According to a further feature of the present invention there areprovided intermediates for the preparation of certain compounds ofgeneral formula I according to the third embodiment of the invention,i.e. compounds for which in their alternative meanings R² represents thehydrogen atom, the formyl or carboxy group, a straight- orbranched-chain alkanoyl group containing from 2 to 6 carbon atoms whichis substituted by one or more halogen atoms, the dithio group (whichjoins two pyrazole rings), the amino group, the --SO₂ Cl group, astraight- or branched-chain carboxyalkyl group containing from 2 to 6carbon atoms, R³ represents the carbamoyl group or a straight- orbranched-chain alkoxycarbonyl group containing from 2 to 7 carbon atomsor the diphenoxycarbonylamino group, R⁴ -R⁸ substitution is a preferredcombination given earlier in the specification and R¹ represents theamino, hydroxymethyl, carboxy or carbamoyl group or a straight- orbranched-chain alkoxycarbonyl or alkoxycarbonylamino group containingfrom 2 to 7 carbon atoms.

The following Examples and Reference Examples illustrate the preparationof compounds of general formula I according to the present invention:

EXAMPLE 33 Compound No. 109

A mixture of 2,4,6-trichlorophenylhydrazine (21.1 g) andtetracyanoethylene (13.3 g) in ethanol (100 ml) was heated at reflux for15 minutes. The reaction mixture was cooled and the solid precipitatewas filtered off and washed with diethyl ether to give5-amino-3,4-dicyano-1-(2,4,6-trichlorophenyl) pyrazole (13 g), as a buffcolored solid, m.p. 267°-271° C.

EXAMPLE 34 Compounds Nos. 110 and 111

Tetracyanoethylene (1.9 g) and2,6-dichloro-4-trifluoromethylphenylhydrazine (3.7 g) was added to amagnetically-stirred solution of sodium acetate (0.6 g) in glacialacetic acid (15 ml) at laboratory temperature. After stirring for 15minutes, a colorless solid precipitated from the solution and stirringwas continued overnight. The mixture was then filtered. The solidobtained was washed successively with acetic acid, water, aqueous sodiumbicarbonate solution and water, to give5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole(2.5 g), as beige crystals, m.p. 221°-222° C.

By proceeding in a similar manner, but replacing the2,6-dichloro-4-trifluoromethylphenylhydrazine by2,3,5,6-tetrachlorophenylhydrazine, there was obtained:

5-Amino-3,4-dicyano-1-(2,3,5,6-tetrachlorophenyl)pyrazole, m.p. greaterthan 330° C., in the form of a buff-colored powder.

REFERENCE EXAMPLE 19

Phenylhydrazines used as starting materials in Examples 33, 34 and 43,not hitherto described in the chemical literature were prepared asfollows:

2,6-Dichloro-4-trifluoromethylphenylaniline (4.3 g) was dissolved withstirring, in glacial acetic acid (23 ml). A solution of sodium nitrite(1.5 g) in concentrated sulphuric acid (11 ml) was then added at 55°-60°C. The solution thus obtained was cooled to 0°-5° C. and a solution ofstannous chloride (16.4 g) in concentrated hydrochloric acid (14 ml) wasadded with vigorous stirring. A cream-colored solid precipitated. Themixture was filtered and the solid obtained was added to a mixture ofaqueous ammonia solution and ice. The mixture thus obtained wasextracted with diethyl ether (6×500 ml) and the combined etherealextracts were dried over sodium sulphate, filtered and evaporated todryness to give 2,6-dichloro-4-trifluoromethylphenylhydrazine (3.7 g)m.p. 54°-56° C., in the form of a colorless crystalline solid.

By proceeding in a similar manner, but replacing the2,6-dichloro-4-trifluoromethylaniline by the hereinafter indicatedaniline there were prepared:

2-Chloro-4-trifluoromethylphenylhydrazine, m.p. 38°-39° C., in the formof a colorless solid, from 2-chloro-4-trifluoromethylaniline.

EXAMPLE 35 Compound No. 112

Ethoxyethylenemalononitrile (44.5 g) and2,6-dichloro-4-trifluoromethylphenylhydrazine (80.0 g) were added to astirred solution of sodium acetate (13.4 g) in glacial acetic acid (110ml) at laboratory temperature. A thick suspension was obtained and wasstirred overnight, after which a dark solution had formed. The solventwas evaporated in vacuo, and the residue was diluted with aqueous sodiumbicarbonate solution (100 ml) and extracted with dichloromethane (3×100ml), and the combined extracts were washed with sodium bicarbonatesolution (50 ml), then with water (100 ml), dried over anhydrousmagnesium sulphate and evaporated in vacuo to give a dark syrup. Thiswas heated at reflux with 2-ethoxyethanol (200 ml) for 1 hour, and thenevaporated in vacuo to give a dark oil. The oil was dissolved indichloromethane, washed with sodium bicarbonate solution (50 ml), thenwith water (100 ml), dried over anhydrous magnesium sulphate, treatedwith charcoal, and evaporated in vacuo to give a black solid. The solidwas recrystallized twice from a mixture of toluene and petrolum ether(b.p. 60°-80° C.) to give5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazole(49.3 g), m.p. 194°-196° C., in the form of pale brown crystals.

EXAMPLE 36 Compounds Nos. 113, 130, 132 and 144

To a mechanically stirred solution of2,6-dichloro-4-trifluoromethylphenylhydrazine (180.3 g) in dry diethylether (700 ml) was added anhydrous potassium carbonate (112 g), and themixture was cooled to 0° C. To this mixture was added dropwise duringhalf-an-hour a solution of2-chloro-1,1-dicyano-2-trifluoromethylethylene (132.1 g) in dry diethylether (350 ml). The ice-bath was removed at the end of the reaction, andthe mixture was left overnight and then poured onto water (2000 ml). Theethereal layer was separated and the aqueous solution extracted withdiethyl ether (2×300 ml). The combined extracts were dried overanhydrous magnesium sulphate, filtered, and evaporated in vacuo to givea buff solid (350 g).

Recrystallization from toluene/hexane gave white crystals (169.5 g) m.p.202°-204° C. of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole.

By proceeding in a similar manner, but replacing the2-chloro-1,1-dicyano-2-trifluoromethylethylene by2-chloro-1-cyano-1-methanesulphonyl-2-trifluoromethylethylene there wasprepared:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-trifluoromethylpyrazolein the form of buff crystals m.p. 215°-218° C., from toluene-hexane.

By proceeding in a similar manner, but replacing the2-chloro-1,1-dicyano-2-trifluoromethylethylene by2-chloro-1-cyano-1-methoxycarbonyl-2-trifluoromethylethylene there wasprepared:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methoxycarbonyl-3-trifluoromethylpyrazolein the form of fawn crystals, m.p. 114°-115° C., from hexane.

By proceeding in a similar manner, but replacing the2,6-dichloro-4-trifluoromethylphenylhydrazine by2,6-dichloro-4-trifluoromethoxyphenylhydrazine there was prepared:

5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-3-trifluoromethylpyrazolein the form of white crystals, m.p. 160°-160.5° C. from toluene-hexane.

EXAMPLE 37 Compounds Nos. 127, 128, 129 and 155

Anhydrous sodium acetate (0.246 g) was added to a stirred solution of2-chloro-1,1-dicyano-2-pentafluoroethylethylene (1.38 g) in acetic acid(5 ml). To this mixture was added2,6-dichloro-4-trifluoromethylphenylhydrazine (1.47 g) during 5 minutes.After stirring overnight the mixture was neutralized with sodiumbicarbonate solution, and extracted with dichloromethane (2×50 ml). Thecombined extracts were washed with water, dried over anhydrous magnesiumsulphate, filtered, and evaporated in vacuo to give a buff solid )2.1 g). This solid was heated under reflux with 2-ethoxyethanol (10 ml) for 1hours, and evaporated in vacuo to give a brown oil (2.2 g). This oil waschromatographed on silica (Merck, 230-400 mesh, 0.7 kg cm⁻²) using amixture of dichloromethane and ethyl acetate (98:2) to give a yellowsolid. Recrystallization from a mixture of dichloromethane and petroleumether gave5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-pentafluoroethylpyrazoleas white crystals, m.p. 160°-162° C.

By proceeding in a similar manner, but replacing the2-chloro-1,1-dicyano-2-pentafluoroethyl-ethylene by2-chloro-1,1-dicyano-2-chlorodifluoromethylethylene there was prepared:

5-Amino-3-chlorodifluoromethyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyanopyrazolein the form of white prisms, m.p. 192° C., from toluenehexane.

By proceeding in a similar manner, but replacing the2-chloro-1,1-dicyano-2-pentafluoroethylethylene by2-chloro-1,1-dicyano-2-difluoromethylethylene there was prepared:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-3-difluoromethylpyrazolein the form of a colorless solid, m.p. 184.5° C. (from toluene-petroleumether).

By proceeding in a similar manner, but replacing the2-chloro-1,1-dicyano-2-pentafluoroethylethylene by2-chloro-1,1-dicyano-2-heptafluoropropylethylene there was prepared:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-3-heptafluoropropylpyrazolein the form of colorless prisms, m.p. 139°-140° C. (fromtoluene-petroleum ether).

REFERENCE EXAMPLE 20

Chloro-dicyanoethylenes used as starting materials in the aboveExamples, not hitherto described in the chemical literature wereprepared by follows:

A suspension of 2-cyano-3-hydroxy-4-chloro-4,4-difluorobut-2-enenitrilesodium salt (18.56 g) in dichloromethane (60 ml) was stirred at roomtemperature and treated with phosphorus pentachloride (19.27 g). Thesuspension was heated under reflux for 6 hours, cooled and filtered, andthe filtrate was distilled. A Widmer fractionating column was used togive 2-chloro-1,1-dicyano-2-chlorodifluoromethylethylene as a liquid,b.p. 88° C. (44 mmHg) (71 g).

By proceeding in a similar manner, but replacing2-cyano-3-hydroxy-4-chloro-4,4-difluorobut-2-enenitrile sodium salt by2-cyano-3-hydroxy-4,4-difluorobut-2-enenitrile sodium salt there wasprepared 2-chloro-1,1-dicyano-2-difluoromethyl-ethylene as a liquid,b.p. 94° C. (46 mmHg).

By replacing 2-cyano-3-hydroxy-4-chloro-4,4-difluorobut-2-enenitrilesodium salt by3-hydroxy-2-methanesulphonyl-4,4,4-trifluorobut-2-enenitrile sodium saltand proceeding in a similar manner there was prepared2-chloro-1-cyano-1-methanesulphonyl-2-trifluoromethylethylene as a palebrown liquid.

By replacing 2-cyano-3-hydroxy-4-chloro-4,4-difluorobut-2-enenitrilesodium salt by3-hydroxy-2-methoxycarbonyl-4,4,4-trifluorobut-2-enenitrile sodium saltand proceeding in a similar manner there was prepared2-chloro-1-cyano-1-methoxycarbonyl-2-trifluoromethylethylene as acolorless oil, b.p. 86°-92° C. at 23-25 mm Hg.

By replacing 2-cyano-3-hydroxy-4-chloro-4,4-difluorobut-2-enenitrilesodium salt by2-cyano-3-hydroxy-4,4,5,5,6,6,6-heptafluorohex-2-enenitrile sodium saltand proceeding in a similar manner there was prepared2-chloro-1,1-dicyano-2-heptafluoropropylethylene as a pale yellowliquid, b.p. 110° C. at 60 mm Hg.

REFERENCE EXAMPLE 21

The sodium salts used in the above Reference Examples as startingmaterials, not hitherto described in the chemical literature, wereprepared as follows:

To a solution of sodium methoxide (5.61 g) in anhydrous methanol (70 ml)was added malononitrile (6.85 g) and the yellow solution treated withmethyl chlorodifluoroacetate (15 g). The mixture was heated under refluxfor 4 hours, the solvent was evaporated in vacuo and reevaporated afteraddition of toluene to give2-cyano-3-hydroxy-4-chloro-4,4-difluoro-but-2-enenitrile sodium salt asa brown solid (18.9 g). This was dried in a vacuum desiccator.

By proceeding in a similar manner, but replacing methylchlorodifluoroacetate by ethyl difluoroacetate there was obtained2-cyano-3-hydroxy-4,4-difluorobut-2-enenitrile sodium salt as a lightbrown solid.

By proceeding in a similar manner, but replacing methylchlorodifuloroacetate by methyl trifluoroacetate, and the malononitrileby methanesulphonylacetonitrile there was obtained3-hydroxy-2-methanesulphonyl-4,4,4-trifluorobut-2-enenitrile sodium saltas a brown solid.

By proceeding in a similar manner, but replacing methylchlorodifuloroacetate by methyltrifluoroacetate, and the malononitrileby methylcyanoacetate there was obtained3-hydroxy-2-methoxycarbonyl-4,4,4-trifluorobut-2-enenitrile sodium saltas a buff solid.

By proceeding in a similar manner, but replacing methylchlorodifluoroacetate by methylheptafluorobutyrate there was obtained2-cyano-3-hydroxy-4,4,5,5,6,6,6-heptafluorohex-2-enenitrile sodium saltas a light brown hygroscopic solid.

EXAMPLE 38 Compound No. 131

To stirred 80% sulphuric acid (22 ml) was added5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(3.98 g) at 80° C. After 1 hour, the cooled solution was poured onto iceand extracted with dichloromethane (3×). The combined extracts werewashed with water, dried over anhydrous magnesium sulphate, filtered,and evaporated in vacuo to give a white solid. This solid wasrecrystallized from ethyl acetate-petroleum ether to give5-amino-4-carbamoyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(3.5 g), m.p. 169°-171° C. in the form of white crystals.

EXAMPLE 39 Compounds Nos. 114, 115 and 116

3,5-Diamino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole(3.9 g); prepared as described below) was dissolved with stirring inglacial acetic acid (60 ml) at 15° C. A solution of sodium nitrite (0.88g) in concentrated sulphuric acid (5.85 ml) was then added over 5minutes, maintaining at 15° C. After 15 minutes longer at thistemperature, the dark red oil solution was poured during 1 minute onto astirred solution of cuprous chloride (2.32 g) in concentratedhydrochloric acid (26 ml). After 15 minutes at laboratory temperature,by which time the evolution of nitrogen had completely subsided, thereaction mixture was poured onto excess ice and water, and extractedwith dichloromethane (3×50 ml). The combined extracts were washed withwater (2×50 ml), then with sodium bicarbonate solution (50 ml), driedover anhydrous magnesium sulphate, and evaporated in vacuo to give abrown semi-solid (4.1 g). Chromatography on silica (Merck, 230-400 mesh,0.7 kg cm⁻²) using a mixture of dichloromethane and ethyl acetate (98:2)as eluent gave after evaporation of the eluate and recrystallization ofthe residue from a mixture of dichloromethane and petroleum ether (b.p.60°-80° C.)5-amino-3-chloro-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole(0.95 g), m.p. 189°-191° C., in the form of white crystals.

By proceeding in a similar manner but replacing the cuprous chloride andconcentrated hydrochloric acid by cuprous bromide and 48% w/vhydrobromic acid respectively there was prepared:

5-Amino-3-bromo-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole,m.p. 182°-183° C., in the form of white crystals.

By replacing the cuprous chloride and concentrated hydrochloric acid bya solution of potassium iodide in water there was prepared:

5-Amino-3-iodo-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole,m.p. 208°-210° C., in the form of white crystals.

REFERENCE EXAMPLE 22

A suspension of 2,6-dichloro-4-trifluoromethylphenylhydrazine (14.7 g)in water (40 ml) was stirred with concentrated hydrochloric acid (5.2ml), and potassium cyanoform (8.52 g) added. The suspension was stirredand heated under reflux for 16 hours, and left to cool overnight. Themixture was washed into a separating funnel with the aid of ethylacetate and water, and the organic phase collected. The aqueous phasewas re-exracted with ethyl acetate (2×80 ml), and the combined organicsolutions washed with water (2×50 ml), dried over anhydrous magnesiumsulphate, and evaporated in vacuo to give an orange solid (20.9 g). Tworecrystallizations from a mixture of ethyl acetate and petroleum ether(b.p.60°-80° C.) gave3,5-diamino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole(7.75 g), m.p. 208°-210° C. in the form of white crystals.

EXAMPLE 40 Compound No. 117

A solution of ethanethiol (2.1 g) in toluene (10 ml) was added dropwiseat 5°-10° C. to a stirred suspension of N-chlorosuccinimide (4.7 g) intoluene (40 ml). The reaction mixture was filtered after 20 minutes togive a solution of ethanesulphenyl chloride. This filtrate was addeddropwise with stirring to a solution of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazolesodium salt [prepared in situ by reaction of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazole(5 g) with sodium hydride (0.4 g)] in tetrahydrofuran (50 ml) containing15-crown-5 (3 drops) at a temperature of 5°-10° C. After 2 hours,aqueous sodium bicarbonate solution (50 ml) was added, and the organicphase was separated and washed with water (2×50 ml), and dried overanhydrous magnesium sulphate. Evaporation of the solvent in vacuo gave adark brown gum, which was chromatographed on silica (Merck 230-400 mesh,0.7 kg cm⁻²) using dichloromethane as eluent. Evaporation of the eluatesgave an orange gum, which then recrystallized from a mixture of ethylacetate and hexane to give4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-5-ethanesulphenylaminopyrazole(2.3 g), m.p. 160°-161° C., in the form of a pale yellow solid.

EXAMPLE 41 Compounds Nos. 118, 119 and 135

A mixture of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazole(5 g) and p-toluenesulphonic acid hydrate (0.1 g) intrimethylorthoformate (20 ml) was heated at reflux for 4.5 hours. Aftercooling, the reaction mixture was evaporated to dryness in vacuo. Theresidue was dissolved in diethyl ether and left to crystallize at 0° C.The dark colored solid was recrystallized from a mixture of ethanol andwater to give4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-5-methoxymethyleneaminopyrazole(4.67 g) m.p. 75°-78° C., in the form of buff crystals.

By proceeding in a similar manner but replacing thetrimethylorthoformate by tripropylorthoformate there was prepared:

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-5-propoxymethyleneaminopyrazole,m.p. 77°-79° C., in the form of buff crystals.

By proceeding in a similar manner but replacing the5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazoleby5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole,and the trimethylorthoformate by triethyl orthoformate, there wasprepared:

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxymethyleneamino-3-trifluoromethylpyrazole,m.p. 160°-162° C., from hexane, in the form of white crystals.

EXAMPLE 42 Compounds Nos. 120, 121, 122, 123, 124, 134 and 133

A suspension of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole(15.0 g) in chloroform (250 ml) was treated with acetyl chloride (42.8ml) with mechanical stirring at 0° C. A solution of dry pyridine (7.0ml) in chloroform (30 ml) was added dropwise during 30 minutes, keepingat 0° C. The mixture was stirred overnight at laboratory temperature,and then heated under reflux conditions in order to complete thereaction. After cooling, the solution was poured onto a mixture of iceand dilute hydrochloric acid, and the chloroform layer separated. Theaqueous solution was re-extracted with chloroform (2×100 ml), and thecombined organic extracts were washed with water (100 ml), dried overanhydrous magnesium sulphate, and evaporated in vacuo to give abuff-colored solid (23.0 g). Recrystallization from a mixture of ethylacetate and petroleum ether (b.p. 60°-80° C.) gave5-acetamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole,m.p. 208°-209° C., in the form of white crystals.

By proceeding in a similar manner, the following phenylpyrazoles wereobtained by acylation of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazolewith the appropriate acid chloride:

5-Dichloroacetamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole,m.p. 186°-187° C. after purification by trituration with carbontetrachloride and subsequent recrystallization from a mixture of ethanoland water, in the form of an off-white solid. The reaction was performedat laboratory temperature.

5-Cyclopropylcarbonamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole,m.p. 217°-218° C. after recrystallization from a mixture of ethanol andwater, in the form of an off-white solid. The reaction was performed atlaboratory temperature.

5-Pentanamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazolein the form of a pale yellow glass. Infra-Red Absorption bands: 3260,3100, 2960, 2940, 2880, 2240, 1730, 1700, 1315, 880 820 cm⁻¹ (liquidfilm). The reaction was performed at 0° C. during the addition, and atlaboratory temperature thereafter.

5-Propionamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole,m.p. 188°-189° C. after purification by chromatography on silica (Merck,230-400 mesh, 0.7 kg cm⁻²) using a mixture of acetone and hexane (2:3)as eluent, and subsequent trituration with toluene, in the form of awhite powder. The reaction was performed at laboratory temperature.

By proceeding in a similar manner, but replacing the solvent byacetonitrile, the following phenylpyrazole was obtained by acylation of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazolewith trimethylacetyl chloride:

1-(2,6-Dichloro-4-trifluoromethylphenyl)-3,4-dicyano-5-(2,2-dimethylpropionamido)pyrazoleas white crystals, m.p. 202°-203° C. from toluene-hexane, and afterpurification by chromatography on silica (Merck, 230-400 mesh, 0.7 kgcm⁻²) using a mixture of dichloromethane and ethyl acetate (9:1) aseluent.

By proceeding in a similar manner but replacing5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole by5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleand by heating under reflux for 18 hours there was obtained:

5-Acetamido-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole,m.p. 225°-227° C., from ethyl acetate-hexane, in the form of whitecrystals.

EXAMPLE 43 Compounds Nos. 125 and 126

Anhydrous sodium acetate (1.0 g) was dissolved in stirred acetic acid(40 ml), and tetracyanoethylene (3.5 g) was added at laboratorytemperature. 2-Chloro-4-trifluoromethylphenylhydrazine (5.25 g) wasadded in one portion, and the mixture was stirred overnight. Afterdilution with water, the precipitated solid was filtered off to give,after drying,5-amino-1-(2-chloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole, m.p.209°-210° C. in the form of a white powder.

By proceeding in a similar manner but replacing the2-chloro-4-trifluoromethylphenylhydrazine by2,3,5,6-tetrafluoro-4-trifluoromethylphenylhydrazine and with coolingduring addition of the phenylhydrazine to the tetracyanoethylenesolution, there was prepared:

5-amino-3,4-dicyano-1-(2,3,5,6-tetrafluoro-4-trifluoromethylphenyl)pyrazole,m.p. 262°-263° C. in the form of a buff powder.

EXAMPLE 44 Compounds Nos. 136 and 137

Sodium hydride (80%, 0.25 g) was added to a stirred solution of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(2.9 g) in dry tetrahydrofuran (50 ml). After 3 hours at roomtemperature, 15-crown-5 (1 drop) and methyl iodide (2 g) was added at 0°C., and the mixture left overnight at room temperature. The solution wasevaporated in vacuo, and the residue was dissolved in dichloromethane(50 ml), washed with water, dilute hydrochloric acid and water. Afterdrying over anhydrous magnesium sulphate, filtration, and evaporation invacuo a yellow oil was obtained. Purification by chromatography usingMerck silica (230-400 mesh, 0.7 kg cm⁻²) with dichloromethane as eluentgave4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dimethylamino-3-trifluoromethylpyrazoleas a white solid, m.p. 105°-107° C.

By proceeding in a similar manner but replacing the methyl iodide byethyl bromoacetate, and employing dioxan as solvent in place oftetrahydrofuran there was obtained4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonylmethylamino-3-trifluoromethylpyrazoleas white crystals, m.p. 104°-106° C. from ethyl acetate-petroleum ether.

EXAMPLE 45 Compound No. 138

To a suspension of4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxymethyleneamino-3-trifluoromethylpyrazole(1.0 g) in methanol (10 ml) stirred at room temperature was added sodiumborohydride (0.17 g). After 2 hours an additional 0.17 g of sodiumborohydride was added, and another 0.34 g added after 1 hours. One hourlater the mixture was poured onto water (80 ml). The combined extractswere dried over anhydrous magnesium sulphate, filtered, and evaporatedin vacuo. The white solid thus obtained was purified by chromatographyon silica (Merck, 230-400 mesh, 0.7 kg cm⁻²) with dichloromethane aseluent, to furnish4-cyano-5-methylamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleas a white solid (0.6 g), m.p. 200°-202° C.

EXAMPLE 46 Compounds Nos. 139, 145 and 146

Sodium hydride (80%, 0.3 g) was added to a stirred solution of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(2.9 g) in dry tetrahydrofuran (50 ml). After 3 hours, 15-crown-5 (1drop) and trimethylacetyl chloride (1.8 g) was added, and the mixturestirred overnight. Evaporation in vacuo gave a buff semisolid, which wasdissolved in dichloromethane. This solution was washed with water,dilute hydrochloric acid and with water again and finally dried overanhydrous magnesium sulphate. Filtration followed by evaporation invacuo gave a yellow oil, which was purified by chromatography on silica(Merck, 40-230 mesh, 0.7 kg cm⁻²). Elution with dichloromethane gaveafter evaporation4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(2,2-dimethylpropionamido)-3-trifluoromethylpyrazoleas a white solid, m.p. 198°-200° C.

By proceeding in a similar manner but replacing the trimethylacetylchloride by ethyl chloroformate there was obtained, afterrecrystallization from toluene,4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-3-trifluoromethylpyrazoleas white crystals, m.p. 62° C.

By proceeding in a similar manner but replacing the trimethylacetylchloride by cyclopropanecarboxylic acid chloride there was obtained4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis-(cyclopropanecarbonyl)amino-3-trifluoromethylpyrazoleas a pale yellow solid, m.p. 126°-127° C.

EXAMPLE 47 Compound No. 147

A solution of4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(cyclopropanecarbonyl)amino-3-trifluoromethylpyrazole(1.0 g) in ethanol (50 ml) was heated under reflux with saturated sodiumbicarbonate solution (25 ml) for 45 minutes. After cooling, andevaporation of the solvent in vacuo, the residue was diluted with waterand extracted with dichloromethane. The extract was dried over anhydrousmagnesium sulphate, filtered, and evaporated in vacuo to give4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-cyclopropanecarbonamido-3-trifluoromethylpyrazoleas a white solid m.p. 210°-212° C.

EXAMPLE 48 Compound No. 141

A stirred mixture of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(3.89 g) and bromoform (13 ml) was treated with tert-butyl nitrite (2.26ml) at room temperature. After 15 minutes the mixture was heated to 50°C. for 1 hour, and evaporated in vacuo to yield a red oil. This waspurified by chromatography on silica (Merck, 40-230 mesh, 0.7 kg cm⁻²)eluting with a mixture of dichloromethane and petroleum ether (1:2) tofurnish5-bromo-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleas a fawn solid m.p. 85°-87° C. (3.7 g).

EXAMPLE 49 Compound No. 142

A solution of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-hydroxymethylpyrazole(1.25 g) in dichloromethane (10 ml) was added slowly to a stirredsolution of diethylaminosulphur trifluoride (0.66 g) in dichloromethane(6 ml) cooled to -78° C. After 30 minutes at this temperature thesolution was warmed to room temperature and stirred for 2 hours. Themixture was then poured onto water (20 ml) and the dichloromethane layerwas separated, dried over anhydrous magnesium sulphate, filtered andevaporated in vacuo. The product was purified by chromatography onsilica (Merck, 40-230 mesh, 0.7 kg cm⁻²) eluting with a mixture ofdichloromethane and ethyl acetate (98:2), and subsequentrecrystallization from dichloromethane-petroleum ether to give5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-fluoromethylpyrazoleas a white solid m.p. 139°-141° C.

REFERENCE EXAMPLE 23

5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-hydroxymethylpyrazolewas prepared as follows:

A solution of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonylpyrazole(1.0 g) in dry tetrahydrofuran (15 ml) was treated under nitrogen withlithium borohydride (0.06 g) with stirring at room temperature for 18hours. Ethyl acetate (5 ml) followed by saturated sodium chloridesolution (5 ml) was added, and the mixture was acidified with dilutehydrochloric acid and extracted with dichloromethane. The extract wasdried over anhydrous magnesium sulphate, filtered, and evaporated invacuo. The residual oil was purified by chromatography on silica (Merck,40-230 mesh, 0.7 kg cm⁻²) eluting with a mixture of dichloromethane andethyl acetate (1:1), and the pure fractions were evaporated in vacuo andrecrystallized from ethyl acetate-petroleum ether to give the titlecompound as a white solid m.p. 159°-161° C.

5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonylpyrazolewas prepared as follows:

To sodium hydride (80%, 0.9 g) in dry ethanol (30 ml) was added, withstirring, malononitrile (1.98 g). Ethylchloro-(2,6-dichloro-4-trifluoromethylphenyl)hydrazono-acetate (11.0 g)was then added with stirring and cooling. The internal temperaturequickly rose to 20° C. and was kept at that for 1 hour, beforefiltration of the pale yellow solid. The filtrate was evaporated invacuo to give an orange solid. The combined solids were dissolved inethyl acetate, washed twice with water, dried over anhydrous magnesiumsulphate, filtered and evaporated in vacuo to give an orange solid (11.0g). Recrystallization from ethyl acetate-petroleum ether gave the titlecompound as fawn crystals (8.3 g) m.p. 208°-209° C.

Ethyl chloro-(2,6-dichloro-4-trifluoromethylphenyl)hydrazonoacetate wasprepared as follows:

Sodium nitrite (3.04 g) was added during 15 minutes to stirredconcentrated sulphuric acid (24 ml) at 30°-50° C. The solution wascooled to 20° C., and added dropwise during 15 minutes to a solution of2,6-dichloro-4-trifluoromethylaniline (9.2 g) in acetic acid (90 ml),maintaining at 35°-40° C. This solution was then cooled to +10°, andadded dropwise to a stirred solution of anhydrous sodium acetate (54 g)and ethyl chloroacetoacetate (7.0 g) in a mixture of water (72 ml) andethanol (48 ml) during 45 minutes with cooling such that the temperaturewas kept at 10° C. After 1 hour at room temperature the mixture wasdiluted with water, filtered, and the solid dissolved indichloromethane. This solution was dried over anhydrous magnesiumsulphate, filtered, and evaporated in vacuo to give tht title compoundas a white solid (11.9 g) m.p. 96°-98° C.

EXAMPLE 50 Compounds 140 and 148

A mixture of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(3.64 g) and N-bromosuccinimide (1.78 g) in carbon tetrachloride (30 ml)was stirred and heated under reflux for 1 hour. FurtherN-bromosuccinimide (0.89 g) was added, and reflux was continued for afurther 1 hour. The mixture was cooled, filtered, and the filtrate wasevaporated in vacuo to give an orange solid. Recrystallization frompetroleum ether gave5-amino-4-bromo-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolein the form of white crystals (2.6 g) m.p. 119°-120° C.

By proceeding in a similar manner but replacing N-bromosuccinimide byN-chlorosuccinimide there was obtained5-amino-4-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleas white crystals m.p. 99°-100° C. No excess of chlorinating agent wasrequired in this case.

REFERENCE EXAMPLE 24

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolewas prepared as follows:

A solution of5-amino-4-carboxy-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(10.5 g) in N,N-dimethylaniline (13 ml) was heated under reflux for 3hours. The cooled mixture was poured onto concentrated hydrochloric acid(15 ml) and extracted with ether (4×30 ml). The combined extract waswashed with 6N hydrochloric acid (3×30 ml), with water (2×30 ml), driedover anhydrous magnesium sulphate, filtered, and evaporated in vacuo.The product was recrystallized from cyclchexane to give the titlecompound (5.7 g) as white needles m.p. 126°-128° C.

5-Amino-4-carboxy-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolewas prepared as follows:

A mixture of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methoxycarbonyl-3-trifluoromethylpyrazole(101.2 g; hereinbefore described in Example 36) and sodium hydroxide (48g) in water (170 ml) and methanol (550 ml) was stirred at roomtemperature for 2 days, evaporated in vacuo, and the residue trituratedwith dilute hydrochloric acid. The solid was filtered, dissolved inethyl acetate, and the resulting solution was washed with sodiumchloride solution. After drying over anhydrous magnesium sulphate,filtration, and evaporation in vacuo a semisolid residue was obtained.This residue was triturated with hexane and the solid was recrystallizedfrom toluene-hexane to give the title compound as a cream solid, m.p.212°-215° C.

EXAMPLE 51 Compound No. 149

Ethyl chloroformate (1.6 g) was added to a stirred solution of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(3.9 g) in pyridine (15 ml). After stirring overnight another additionof ethyl chloroformate (1.0 ml) was made, and the mixture was left for afurther 12 hours. The solvent was evaporated in vacuo and the residuewas acidified with dilute hydrochloric acid, and extracted withdichloromethane. This extract was washed with water (3×), dried overanhydrous magnesium sulphate, filtered, and evaporated in vacuo.Purification by chromatography on silica (Merck, 40-230 mesh, 0.7 kgcm⁻²) eluting with ethyl acetate - petroleum ether (1:1) gave a whitesolid, which was recrystallized from a mixture of dichloromethane andhexane to furnish white crystals of4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonylamino-3-trifluoromethylpyrazole,m.p. 177°-179° C.

EXAMPLE 52 Compound No. 143

A solution of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(3.0 g) in concentrated sulphuric acid (10 ml) at 0° C. was treated withfuming nitric acid (9 ml) during 15 minutes, keeping the temperature at5°-15° C. After 30 minutes the mixture was poured onto excess ice, andthe precipitated solid was filtered off and dissolved in ethyl acetate.After drying over anhydrous magnesium sulphate, filtration, andevaporation in vacuo a brown oil was obtained. This oil was dissolved inthe minimum of ethyl acetate and diluted with hexane. A pale yellowsolid crystallized and this was discarded. The filtrate was evaporatedin vacuo to give a solid which was recrystallized from toluene-hexane tofurnish a yellow solid. One further recrystallization from the samesolvent pair gave5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethylpyrazoleas white crystals, m.p. 214°-215° C.

EXAMPLE 53 Compound No. 150

To a solution of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(2.33 g) in dry tetrahydrofuran (30 ml) was added with stirring at roomtemperature, a solution of tert-butyl nitrite (1.36 ml) in drytetrahydrofuran (5 ml) during 2 minutes. The solution was then heatedunder reflux for 1 hour and cooled, and additional tert-butyl nitrite(2.72 ml) was added. The solution was heated under reflux for 30minutes, and left to cool overnight. Evaporation in vacuo gave an orangeoil, which was purified by chromatography on silica (Merck, 40-230 mesh,0.7 kg cm⁻²) eluting with dichloromethane-hexane (1:1). The product wasfinally recrystallized from hexane to give4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole,m.p. 121°-123° C., as white crystals.

EXAMPLE 54 Compound No. 151

To a solution of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(2.33 g) in chloroform (30 ml) stirred at room temperature, was addediodine (3.0 g) followed by tert-butyl nitrite (1.1 g). After 2 hours themixture was heated under reflux for 1.5 hours, cooled and filtered, andthe filtrate was washed with sodium thiosulphate solution to removeexcess iodine. After washing with water, drying over anhydrous magnesiumsulphate and evaporation in vacuo, a yellow solid was obtained. This waschromatographed on silica (Merck, 40-230 mesh, 0.7 kg cm⁻²) eluting withdichloromethane-hexane (1:2) to give a yellow oil. Dissolution in hothexane gave, on cooling,4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-iodo-3-trifluoromethylpyrazoleas white crystals, m.p. 86°-87° C.

EXAMPLE 55 Compound No. 152

To dry diisopropylamine (0.135 g) in dry tetrahydrofuran (4 ml) stirredat -78° C. under nitrogen, was added via a syringe, a solution ofn-butyl lithium (0.52 ml of a 2.6M solution in hexane). After warming toroom temperature during 1 minute, the solution was re-cooled to -78° C.,and added via a syringe to a stirred solution of4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(0.5 g) in dry tetrahydrofuran (4 ml) under nitrogen at -78° C. Theaddition, during 2 minutes, was exothermic and the internal temperaturewas maintained at -60° C. for a further 15 minutes. Methyl iodide (0.1ml) was added. After 1.5 hours at this temperature the solution waspoured onto excess water and extracted with dichloromethane (3×). Thecombined organic phase was washed with water, dried over anhydrousmagnesium sulphate, and evaporated in vacuo to give a solid.Chromatography on silica (Merck, 40-230 mesh, 0.7 kg cm⁻²) eluting withdichloromethane-hexane (1:3) gave a white solid (0.2 g).Recrystallization from hexane furnished4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methyl-3-trifluoromethylpyrazoleas white crystals, m.p. 90°-92° C.

EXAMPLE 56 Compound No. 153

A mixture of5-amino-4-chlorosulphonyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(1.2 g) and dimethylamine (17.6 ml of a 40% aqueous solution) was heatedon a steambath for 1 hour, cooled, and poured onto crushed ice (50 g) togive a brown solid. This solid was filtered, dried, and recrystallizedfrom toluene to give5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(N,N-dimethylsulphamoyl)-3-trifluoromethylpyrazole(0.8 g) as light brown crystals, m.p. 177.6°-178.6° C.

REFERENCE EXAMPLE 25

5-Amino-4-chlorosulphonyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleused in the above example was prepared as follows:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(9.1 g) was added portion-wise to stirred cooled chlorosulphonic acid(16.2 ml), keeping the internal temperature below 10° C. The orangesolution was stirred at room temperature for 30 minutes, then at 120° C.for 5 hours, and poured onto iced water (300 ml) to give a pale brownsolid. This solid was filtered, dried, and recrystallized fromcyclohexane to give the title compound as yellow crystals.

EXAMPLE 57 Compound No. 154

A solution of 2,6-dichloro-4-trifluoromethylphenylhydrazine (3.8 g) and1,1-dicyano-2-cyclopropyl-2-methoxyethylene (2.23 g) in methanol (30 ml)was stirred and treated with sodium hydride (80%, 30 mg). After 4 hoursthe solution was evaporated in vacuo and the residue was dissolved inethyl acetate (40 ml), treated with charcoal and washed with water. Theorganic phase was evaporated in vacuo, the residual oil was dissolved inpetroleum ether and crystals of5-amino-4-cyano-3-cyclopropyl-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole,m.p. 197°-199° C., were obtained.

EXAMPLE 58 Compound Nos. 156, 157 and 158

By proceeding in a similar manner to that hereinbefore described inExample 33, but replacing 2,4,6-trichlorophenylhydrazine by2,6-dichloro-4-trifluoromethylthiophenylhydrazine, there was obtained:

5-Amino-3,4-dicyano-1-(2,6-dichloro-4-trifluoromethylthiophenyl)pyrazole,m.p. 226°-227° C., in the form of an off-white solid, afterrecrystallization from toluene.

By employing 2-chloro-3,5,6-trifluoro-4-trifluoromethylphenylhydrazinethere was prepared:

5-Amino-1-(2-chloro-3,5,6-trifluoro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole,m.p. 242°-243° C., in the form of an orange solid, afterrecrystallization from a mixture of ethanol and water.

By employing 2,6-dichloro-3,5-difluoro-4-trifluoromethylphenylhydrazinethere was prepared:

5-Amino-1-(2,6-dichloro-3,5-difluoro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole,m.p. 245°-247° C., in the form of an off-white solid.

REFERENCE EXAMPLE 26

2,6-Dichloro-4-trifluoromethylthiophenylhydrazine was prepared byfollowing the procedure of Reference Example 19, by proceeding in asimilar manner, but replacing the 2,6-dichloro-4-trifluoromethylanilineby 2,6-dichloro-4-trifluoromethylthioaniline.

REFERENCE EXAMPLE 27

2-Chloro-3,5,6-trifluoro-4-trifluoromethylphenylhydrazine was preparedas follows:

3-Chloro-2,4,5,6-tetrafluorobenzotrifluoride (12.1 g) and hydrazinehydrate (3.4 g) were heated under reflux with ethanol (50 ml) for 3.5hours. The mixture was poured onto ice/water mixture (500 ml), stirred,and the product was filtered. After washing with water and drying in adesiccator the title compound was obtained in the form of whitecrystals, m.p. 91°-92° C.

By proceeding in a similar manner but replacing3-chloro-2,4,5,6-tetrafluorobenzotrifluoride by3,5-dichloro-2,4,6-trifluorobenzotrifluoride there was prepared2,6-dichloro-3,5-difluoro-4-trifluoromethylphenylhydrazine in the formof pale yellow crystals, m.p. 78°-80° C.

EXAMPLE 59 Compound No. 159

By proceeding in a similar manner to that hereinbefore described inExample 2, but employing 2,6-dichloro-4-trifluoromethoxyphenylhydrazinethere was obtained:

5-Amino-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-3,4-dicyanopyrazole,m.p. 231°-232° C. in the form of a brown solid, after recrystallizationfrom toluene.

REFERENCE EXAMPLE 28

2,6-Dichloro-4-trifluoromethoxyphenylhydrazine used in the above Example59 was prepared by following the procedure of Reference Example 19, byproceeding in a similar manner, but replacing the2,6-dichloro-4-trifluoromethylaniline by2,6-dichloro-4-trifluoromethoxyaniline. The title compound was obtainedas fawn crystals, m.p. 64°-65° C.

EXAMPLE 60 Compounds Nos. 160, 161, 162 and 163

By proceeding in a similar manner to that hereinbefore described inExample 5, but replacing the ethoxyethylenemalononitrile byethoxypropylenemalononitrile there was prepared:

5-Amino-4-cyano-3-ethyl-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazolein the form of white crystals, m.p. 158°-160° C., afterrecrystallization from a mixture of ethyl acetate and hexane.

By proceeding in a similar manner but replacing theethoxyethylenemalononitrile byethoxyethylenemethanesulphonylacetonitrile, and by replacing the sodiumacetate and glacial acetic acid by ethanol containing 10 mole percent oftriethylamine at reflux, there was prepared:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-methylpyrazolein the form of a white solid, m.p. 195° C., after recrystallization froma mixture of ethyl acetate and hexane.

By proceeding in a similar manner but replacing theethoxyethylenemalononitrile by ethoxyethylenecyanoacetic acid ethylester there was prepared:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-ethoxycarbonylpyrazolein the form of white crystals, m.p. 115°-118° C. after recrystallizationfrom a mixture of toluene and petroleum ether.

By proceeding in a similar manner but replacing theethoxyethylenemalononitrile byethoxyethylenemethanesulphonylacetonitrile, and by replacing the2,6-dichloro-4-trifluoromethylphenylhydrazine by2,6-dichloro-4-trifluoromethoxyphenylhydrazine and by performing thereaction in a 1:1 v/v mixture of ethanol and triethylamine at ambienttemperature, there was obtained:

5-Amino-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-methanesulphonyl-3-methylpyrazole,in the form of a fawn solid, m.p. 180°-181° C.

REFERENCE EXAMPLE 29

3-Ethoxy-2-methanesulphonylbut-2-ene-nitrile, used in the above Example60 was prepared as follows:

A mixture of methanesulphonylacetonitrile (200 g), triethylorthoacetate(348 g) and zinc chloride (21 g) was stirred in hexane (1200 ml) withheating under reflux. The distillate was collected via a McIntyre head,with additional hexane added to the reaction mixture as necessary.Hexane (2800 ml) was collected during 8 hours. After cooling, themixture was evaporated in vacuo, and re-evaporated after addition oftoluene (100 ml). The residue was dissolved in ethyl acetate andrecrystallized from a mixture of ethyl acetate with hexane, twice., togive white crystals, m.p. 99° C., of the title compound.

EXAMPLE 61 Compounds Nos. 164, 165, 166 and 167

By proceeding in a similar manner to that hereinbefore described inExample 36, but replacing the2,6-dichloro-4-trifluoromethylphenylhydrazine by2-chloro-3,5,6-trifluoro-4-trifluoromethylphenylhydrazine there wasobtained:

5-Amino-1(2-chloro-3,5,6-trifluoro-4-trifluoromethylphenyl)-4-cyano-3-trifluoromethylpyrazole,in the form of white crystals, m.p. 187°-189° C., afterrecrystallization from toluene.

By employing 2,6-dichloro-4-trifluoromethylthiophenylhydrazine there wasobtained:

5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylthiophenyl)-3-trifluoromethylpyrazole,in the form of pale yellow crystals, m.p. 133.5°-134.5° C., afterrecrystallization from hexane.

By replacing the 2-chloro-1,1-dicyano-2-trifluoromethylethylene by2,3-dichloro-1,1-dicyano-3-fluoromethylethylene there was obtained:

5-Amino-3-chlorofluoromethyl-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazolein the form of a cream solid, m.p. 186°-188° C., after recrystallizationfrom a mixture of toluene and hexane.

By employing 2,6-dichloro-3,5-difluoro-4-trifluoromethylphenylhydrazinethere was obtained:

5-Amino-4-cyano-1-(2,6-dichloro-3,5-difluoro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolein the form of a light brown solid, m.p. 176°-177° C.

REFERENCE EXAMPLE 30

Chloro-dicyanoethylene used as starting material in the above Example61, not hitherto described in chemical literature was prepared asfollows:

By proceeding in a similar manner to that hereinbefore described inReference Example 20, but replacing2-cyano-3-hydroxy-4-chloro-4,4-difluorobut-2-enenitrile sodium salt by2-cyano-3-hydroxy-4-chloro-4-fluorobut-2-enenitrile sodium salt therewas prepared 2-chloro-2-chlorofluoromethyl-1,1-dicyanoethylene as aliquid, b.p. 90° C. (46 mmHg).

By proceeding in a similar manner to that hereinbefore described inReference Example 21, but replacing methyl chlorodifluoroacetate byethyl chlorofluoroacetate, there was obtained2-cyano-3-hydroxy-4-chloro-4-fluorobut-2-enenitrile sodium salt as anorange-red solid.

EXAMPLE 62 Compound 168

By proceeding in a similar manner to that hereinbefore described inExample 41, but replacing the trimethylorthoformate bytriethylorthoacetate there was prepared:

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(1-ethoxyethylideneamino)-3-methylpyrazoleas a white solid, m.p. 50°-53° C., after purification by chromatographyon silica (Merck 230-400 mesh, 0.7 kg cm⁻²) using dichloromethane aseluent.

EXAMPLE 63 Compounds Nos. 169, 170 and 171

By proceeding in a similar manner to that hereinbefore described inExample 42, but replacing the5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole by5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-3-methylpyrazoleand acylating with succinyl dichloride there was obtained:

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-5-succinimidopyrazolein the form of a white solid, m.p. 202°-204° C., after purification bychromatography on silica (Merck 230-400 mesh, 0.7 kg cm⁻²) usingdichloromethane/ethyl acetate (98:2) as eluent.

By proceeding in a similar manner but replacing the5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole by5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-trifluoromethylpyrazole,and employing acetonitrile as solvent for the acylation, there wasprepared:

5-Acetamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-trifluoromethylpyrazolein the form of a white solid, m.p. 194°-195° C., after recrystallizationfrom toluene.

By proceeding in a similar manner (to Example 42) but replacing the5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole by5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-methanesulphonylpyrazolethere was prepared5-acetamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-methanesulphonylpyrazolein the form of yellow crystals, m.p. 202°-203° C.

EXAMPLE 64 Compound No. 172

By proceeding in a similar manner to that hereinbefore described inExample 43, but replacing the 2-chloro-4-trifluoromethylphenylhydrazineby 2,6-dichloro-4-nitrophenylhydrazine there was prepared:

5-Amino-1-(2,6-dichloro-4-nitrophenyl)-3,4-dicyanopyrazole, in the formof a pale brown solid, m.p. 289°-290° C.

EXAMPLE 65 Compounds Nos. 173 and 174

By proceeding in a similar manner to that hereinbefore described inExample 44, but replacing the5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazoleand using an appropriate quantity of methyl iodide there was prepared:

1-(2,6-Dichloro-4-trifluoromethylphenyl)-3,4-dicyano-5-methylaminopyrazolein the form of a pale yellow solid, m.p. 165°-166° C., afterrecrystallization from toluene.

By proceeding as above, but employing ethyl iodide, there was prepared:

1-(2,6-Dichloro-4-trifluoromethylphenyl)-3,4-dicyano-5-ethylaminopyrazolein the form of an off-white solid, m.p. 245°-246° C., after purificationby chromatography on silica (Merck 230-400 mesh, 0.7 kg cm⁻²) using amixture of ethyl acetate and petroleum ether (15:85).

EXAMPLE 66 Compounds Nos. 175, 176, 177, 178, 179, 180, 181, 182, 183,184, 185 and 186

By proceeding in a similar manner to that hereinbefore described inExample 46, but replacing the5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleand the trimethylacetyl chloride by the following phenylpyrazoles andacylating agents, there were prepared:

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(N-methyl-N-ethoxycarbonylamino)-3-trifluoromethylpyrazolein the form of a white solid, m.p. 88°-90° C., after recrystallizationfrom hexane, using4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methylamino-3-trifluoromethylpyrazoleand ethyl chloroformate;

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(N-acetyl-N-trimethylacetylamino)-3-trifluoromethylpyrazolein the form of an off-white solid, m.p. 83.5°-34° C., afterrecrystallization from hexane, using4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-trimethylacetylamino-3-trifluoromethylpyrazoleand acetyl chloride;

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(N-propionyl-N-trimethylacetylamino)-3-trifluoromethylpyrazolein the form of a white solid, m.p. 56°-56.5° C., after recrystallizationfrom hexane, using4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-trimethylacetylamino-3-trifluoromethylpyrazoleand propionyl chloride;

1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethyl-5-trimethylacetylaminopyrazolein the form of a white solid, m.p. 219° C., using5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethylpyrazoleand trimethylacetyl chloride;

1-(2,6-Dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonylamino-4-nitro-3-trifluorormethylpyrazolein the form of pale yellow crystals, m.p. 124° C., using5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethylpyrazoleand ethyl chloroformate;

and3-Chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-5-trimethylacetylaminopyrazole,in the form of a white solid, m.p. 203°-204° C.;

3-Chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-5-bis(ethoxycarbonyl)aminopyrazole,in the form of an orange crystalline solid, m.p. 67°-69° C.;

and3-Chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-5-ethoxycarbonylaminopyrazole,in the form of a yellow solid m.p. 175°-179° C.;

[(The latter three compounds were obtained by reaction of5-amino-3-chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyanopyrazolewith the appropriate acyl chlorides)]

4-Cyano-5-diacetylamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolein the form of white crystals, m.p. 138°-139° C.; and

5-(N-Acetyl-N-ethoxycarbonylamino)-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolein the form of a white solid, m.p. 101°-102° C.;

[(The above two compounds were obtained by reaction of5-acetylamino-1-(2,6-dichloro-4-trifluoromethyl)-4-cyano-3-trifluoromethylpyrazoleand the appropriate acyl chlorides] and

1-(2,6-Dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-3,4-dicyanopyrazoleand1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-4-methanesulphonyl-3-trifluoromethylpyrazolewere prepared in a similar manner to the procedure described in Example46, but replacing the5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazoleand by5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-trifluoromethylpyrazolerespectively. The trimethylacetyl chloride was replaced by theappropriate quantity of ethyl chloroformate (two equivalents) and 2equivalents of sodium hydride were also used. The products were whitecrystals with m.p. 74°-76° C., and 148°-151° C., respectively.

EXAMPLE 67 Compounds Nos. 187 and 188

By proceeding in a similar manner to that hereinbefore described inExample 47, but replacing the4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(cyclopropanecarbonyl)amino-3-trifluoromethylpyrazoleby1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-4-methanesulphonyl-3-trifluoromethylpyrazolethere was obtained:

1-(2,6-Dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonylamino-4-methanesulphonyl-3-trifluoromethylpyrazolein the form of a white solid, m.p. 138°-141° C.

By proceeding in a similar manner but replacing the4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(cyclopropanecarbonyl)amino-3-trifluoromethylpyrazoleby1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(ethoxycarbonyl)amino-3,4-dicyanopyrazolethere was obtained:

1-(2,6-Dichloro-4-trifluoromethylphenyl)-3,4-dicyano-5-ethoxycarbonylaminopyrazolein the form of a white solid, m.p. 161°-163° C.

EXAMPLE 68 Compounds Nos. 189 and 190

By proceeding in a similar manner to that hereinbefore described inExample 50, but replacing N-bromosuccinimide by N-iodosuccinimide therewas obtained:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-iodo-3-trifluoromethylpyrazolein the form of a white solid, m.p. 129° C.

By replacing N-bromosuccinimide by N-iodosuccinimide, and replacing5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethlypyrazoleby 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazole(hereinafter described in Reference Example 31), there was obtained:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-iodo-3-methylpyrazolein the form of a buff solid, m.p. 108°-109° C., after recrystallizationfrom hexane.

REFERENCE EXAMPLE 31

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazole wasprepared as follows:

5-Amino-4-carboxy-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazole(28 g) was heated to 190° C. under nitrogen, and maintained at thistemperature until gas evolution ceased. After cooling, the titlecompound was obtained (22 g) as a yellow gum.

5-Amino-4-carboxy-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazoleused above was prepared by proceeding in a similar manner to ReferenceExample 24 but replacing5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methoxycarbonyl-3-trifluoromethylpyrazoleby5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethoxycarbonyl-3-methylpyrazole(hereinbefore described in Example 60), and by performing the basehydrolysis at the reflux temperature in ethanol for 13 hours. The titlecompound was obtained as a white solid, m.p. 183°-184° C.

EXAMPLE 69 Compounds Nos. 191, 192 and 193

By proceeding in a similar manner to that herein before described inExample 52, but replacing5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazole,and replacing the mixture of concentrated sulphuric and fuming nitricacids by concentrated nitric acid alone, there was obtained:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-nitropyrazolein the form of orange crystals, m.p. 229°-231° C., afterrecrystallization from a mixture of toluene and petroleum ether.

By proceeding in a similar manner but replacing5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby5-acetamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole,and replacing the mixture of concentrated sulphuric and fuming nitricacids by a mixture of acetic acid and acetic anhydride to which wasadded fuming nitric acid, there was obtained:

5-Acetamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethylpyrazolein the form of a cream solid, m.p. 194°-195° C.

By proceeding in a similar manner but replacing5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole,and replacing the mixture of concentrated sulphuric and fuming nitricacids by acetic anhydride to which was added fuming nitric acid, therewas obtained:

1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethylpyrazolein the form of an orange solid, m.p. 110°-112° C., afterrecrystallization from a mixture of toluene and hexane.

REFERENCE EXAMPLE 32

1-(2,6-Dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole usedin the above Example 69 was prepared by the procedure described inExample 53 by replacing5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethlpyrazoleby5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole.The title compound was obtained as a pale yellow oil.

5-Acetamido-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleused in the above Example 69 was prepared by the procedure described inExample 47, but replacing the4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(cyclopropanecarbonyl)amino-3-trifluoromethylpyrazoleby5-bis(acetyl)amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole.The title compound was obtained as white crystals, m.p. 142°-144° C.,after recrystallization from ethyl acetate and hexane.

5-Bis(acetyl)amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole,used above, was prepared by the procedure of Example 51 but replacing5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole,and the ethyl chloroformate by acetyl chloride. The title compound wasobtained as a white solid, m.p. 130°-131° C.

EXAMPLE 70 Compounds Nos. 194, 195 and 196

By proceeding in a similar manner to that hereinbefore described inExample 53, but replacing the5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-methanesulphonylpyrazole,there was obtained1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-methylsulphonylpyrazolein the form of yellow crystals, m.p. 168°-169° C.

By proceeding in a similar manner but replacing the5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-fluoropyrazole,there was obtained4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-fluoropyrazole in theform of white crystals, m.p. 120°-121° C.

1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-trifluoromethylpyrazolewas prepared in a similar manner by replacing5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonyl-3-trifluoromethylpyrazole.The title compound was obtained in the form of white needles, m.p.154°-155° C.

EXAMPLE 71 Compound No. 197

By proceeding in a similar manner to that hereinbefore described inExample 54, but replacing the iodine by anhydrous cupric chloride, andby replacing the chloroform by anhydrous acetonitrile, there wasobtained:

5-Chloro-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-3-trifluoromethylpyrazolein the form of a yellow oil, after purification by chromatography onsilica (Merck, 40-230 mesh, 0.7 kg cm⁻²) eluting with a mixture ofdichloromethane and hexane (1:2) Infra-Red Absorption bands: 2260, 1495,1405, 1325, 1160 cm⁻¹ (liquid film).

EXAMPLE 72 Compounds Nos. 198 and 199

By proceeding in a similar manner to that hereinbefore described inExample 56, but replacing the dimethylamine by the appropriate aminesthere was prepared the following phenylpyrazoles:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(N-ethylsulphamoyl)-3-trifluoromethylpyrazolein the form of a cream solid, m.p. 200° C., after recrystallization froma mixture of toluene and petroleum ether.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(N-methylsulphamoyl)-3-trifluoromethylpyrazolein the form of a light brown solid, m.p. 199°-200° C., afterrecrystallization from toluene.

EXAMPLE 73 Compounds Nos. 200 and 201

Trifluoroacetic anhydride (3.5 ml) was added dropwise to a stiffedmixture of 85% w/v hydrogen peroxide solution (0.56 ml) indichloromethane (15 ml) maintaining at 0°-10° C. After warming to 20° C.during 5 minutes, a solution of3-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyanopyrazole (1.0 g;hereinafter described in Reference Example 33) in dichloromethane (10ml) was added dropwise over 5 minutes. A temperature rise of 10° C. wasobserved during the addition, and the mixture heated under reflux for1.5 hours. After cooling, the solution was poured onto excess water, andthe organic solution washed in turn with solutions of sodium bicarbonateand sodium bisulphite. Drying over anhydrous magnesium sulphate,followed by evaporation in vacuo gave a buff solid, which was purifiedby chromatography on silica (Merck, 40-230 mesh, 0.7 kg cm⁻²) elutingwith dichloromethane. The resultant white solid was recrystallized froma mixture of dichloromethane and hexane to give1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-3-nitropyrazole aswhite crystals (0.7 g), m.p. 163°-165° C.

By proceeding in a similar manner but replacing3-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyanopyrazole by5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyanopyrazole(hereinbefore described in Example 34), there was obtained:

1-(2,6-Dichloro-4-trifluoromethylphenyl)-3,4-dicyano-5-nitropyrazole asorange crystals, m.p. 138°-140° C., after recrystallization fromcyclohexane.

REFERENCE EXAMPLE 33

3-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyanopyrazole wasprepared as follows:

A solution of3-tert-butoxycarbonylamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyanopyrazole(2.8 g) in ethanol (100 ml) was treated with 50% v/v hydrochloric acid(10 ml), and the mixture heated under reflux for 1 hour. After standingovernight at room temperature, sodium carbonate was added to pH 8, andthe mixture extracted three times with dichloromethane. The extract waswashed with water, dried over anhydrous magnesium sulphate, andevaporated in vacuo to give a buff solid. Recrystallization from amixture of ethyl acetate and petroleum ether gave the title compound(1.4 g) in the form of white crystals, m.p. 159°-160° C.

3-tert-Butoxycarbonylamino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyanopyrazolewas prepared as follows:

A mixture of3-carboxy-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole (11g) and thionyl chloride (35 ml) and N,N-dimethylformamide (3 drops) washeated under reflux for 2 hours. The solvent was evaporated in vacuo,and re-evaporated in vacuo after addition of dry toluene (20 ml). Theresultant gum was dissolved in dry acetone (50 ml) and stirred, while asolution of sodium azide (2.9 g) in water (15 ml) was added during 5minutes keeping at 10°-15° C. After 30 minutes the mixture was pouredonto water (250 ml) and extracted with dichloromethane (3×80 ml). Thecombined extract was washed with water, dried over anhydrous magnesiumsulphate, and evaporated in vacuo at equal to or below 40° C. to give abuff solid (13 g).

The resulting azide was dissolved in dry toluene (200 ml) and heatedunder reflux for half-an-hour, with smooth evolution of nitrogen. Aftercooling, this was treated with tert-butanol (40 g), and the mixtureheated under reflux overnight. After evaporation in vacuo, the resultingbrown oil (15 g) was purified by chromatography on silica (Merck,230-400 mesh, 0.7 kg cm⁻²) eluting with dichloromethane and ethylacetate (98:2) to give the title compound (8.0 g) as a white solid, m.p.154°-155° C.

3-Carboxy-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole wasprepared as follows:

A suspension of4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonylpyrazole(5.0 g) in ethanol (100 ml) was treated with a solution of sodiumhydroxide (0.63 g) in water 15 ml) and stirred at room temperature for1.5 hours. After evaporation in vacuo at equal to or below 40° C., theresidue was dissolved in water (150 ml) and extracted withdichloromethane (1×100 ml). This extract was back-washed with water(2×50 ml), and the combined aqueous solutions brought to pH 1 withdilute hydrochloric acid, and then extracted with ethyl acetate (3×50ml). This extract was dried over anhydrous magnesium sulphate, andevaporated in vacuo to give a buff solid (4.6 g). Recrystallization froma mixture of toluene and hexane gave the title compound in the form ofbuff crystals (4.4 g), m.p. 203°-205° C.

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonylpyrazolewas prepared by following the method described in Example 53, andreplacing5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonylpyrazole.The title compound was obtained in the form of buff crystals, m.p.198°-199° C.

EXAMPLE 74 Compounds Nos. 202, 203 and 204

Silver (I) fluoride (5 g) was added in portions during 40 minutes to avigorously stirred solution of 1,1-dichloro-2,2-dicyanoethylene inacetonitrile (15 ml), maintained at 0°-10° C. by external cooling. Thestirring was continued at room temperature for 1 hour and the solidfiltered off. The filtrate containing 1,1-difluoro-2,2-dicyanoethylenewas stirred and cooled while a solution of2,6-dichloro-4-trifluoromethylphenylhydrazine (4.9 g) in acetonitrile(15 ml) was added dropwise at 5° C. After stirring overnight the solidwas filtered off and the filtrate evaporated in vacuo to give a darkorange oil (6 g). This was purified by chromatography or silica (Merck,230-400 mesh, 10 lb in⁻²) eluting with dichloromethane to give a whitesolid. Recrystallization from a mixture of cyclohexane and ethyl acetategave5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-3-fluoropyrazole(0.9 g) as a white solid, m.p. 193°-194° C.

By proceeding in a similar manner but replacing the2,6-dichloro-4-trifluoromethylphenylhydrazine by2,6-dichloro-4-trifluoromethoxyphenylhydrazine and by employing1,1-dichloro-2,2-dicyanoethylene instead of1,1-difluoro-2,2-dicyanoethylene, and by using diethyl ether as solvent,there was prepared5-amino-3-chloro-1-(2,6-dichloro-4-trifluoromethoxyphenyl)-4-cyanopyrazolein the form of a yellow solid, m.p. 175°-177° C.

By proceeding as immediately above but replacing the2,6-dichloro-4-trifluoromethoxyphenylhydrazine by2,6-dichloro-3,5-difluoro-4-trifluoromethylphenylhydrazine, there wasprepared5-amino-3-chloro-4-cyano-1(2,6-dichloro-3,5-difluoro-4-trifluoromethylphenyl)pyrazole,in the form of yellow crystals, m.p. 206°-208° C.

EXAMPLE 75 Compounds Nos. 205, 206, 207, 208, 209, 210 and 211

A stirred solution of4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(1.5 g) in dry tetrahydrofuran cooled to -78° C. was treated with asolution of n-butyl lithium (2.6M in hexane, 1.71 ml) dropwise undernitrogen. The temperature was kept below -65° C. during the addition,and the resultant solution kept at -78° C. for 1 hour. A solution oftrimethylsilyl chloride (0.56 ml) in dry tetrahydrofuran (2 ml) was thenadded, dropwise, during 2 minutes. The mixture was allowed to reach roomtemperature over 2 hours, left overnight and evaporated in vacuo to givea pale yellow solid. This was dissolved in dichloromethane, washed withwater, dried over anhydrous magnesium sulphate, and evaporated in vacuo.The product was recrystallized from hexane to give4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethyl-5-trimethylsilylpyrazoleas white crystals, m.p. 108°-110° C.

By proceeding in a similar manner but replacing the trimethylsilylchloride by the reagents listed below, the following phenylpyrazoleswere obtained:

5-tert-Butyldimethylsilyl-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazolein the form of white crystals, m.p. 113°-115° C.; from tertbutyldimethylsilyl chloride.

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methylthio-3-trifluoromethylpyrazole,in the form of a white power, m.p. 73°-74° C.; from methylthiocyanate.

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethyl-5-trifluoromethylthiopyrazole,in the form of white crystals, m.p. 120°-122° C.; frombis(trifluoromethyl)disulphide.

5-Carboxy-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole,in the form of a white solid, m.p. 177°-179° C., by pouring thelithiated pyrazole solution onto a large excess of powdered solid carbondioxide.

By proceeding in a similar manner but replacing the4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethylpyrazole,there was prepared:

1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-nitro-3-trifluoromethyl-5-trimethylsilylpyrazole,in the form of a pale green solid, m.p. 101°-103° C.

By proceeding in a similar manner but replacing the4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methyl-3-trifluoromethylpyrazole(hereinbefore described in Example 55), there was prepared:

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethyl-5-trimethylsilylmethylpyrazole,in the form of a colorless oil. Infra-Red Absorption bands: 2250, 1400,1325, 1260, 1180, 1150, 860 cm⁻¹ (liquid film) Nuclear MagneticResonance: chemical shift (delta) for --Si--CH₂ -- 2.8 ppm indimethylsulphoxide-D⁶.

EXAMPLE 76 Compound No. 212

Sodium methoxide (0.3 g) was added to an ice cold stirred mixture of4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(phenoxycarbonyl)amino-3-trifluoromethylpyrazole(3.1 g) in methanol (30 ml), and heated under reflux for 2 hours. Thiswas poured onto water (200 ml) and extracted with dichloromethane. Theorganic solution was washed with sodium carbonate solution, then withwater, dried over anhydrous magnesium sulphate, and evaporated in vacuo.The resultant white solid was4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methoxycarbonylamino-3-trifluoromethylpyrazole,m.p. 182°-183° C.

REFERENCE EXAMPLE 34

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis-(phenoxycarbonyl)amino-3-trifluoromethylpyrazoleused in the above Example 76 was prepared by following the procedure ofExample 46, but replacing trimethylacetyl chloride by phenylchloroformate. The title compound was obtained as a white solid, m.p.168°-169° C.

EXAMPLE 77 Compounds Nos. 213 and 214

5-Carbamoyl-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(3.57 g) was heated to 200° C. with phosphorus pentoxide (2.82 g) withstirring. After 3 hours, the cooled product was treated with ice, andextracted with dichloromethane (3×50 ml). The organic solution waswashed with water, dried over anhydrous magnesium sulphate, andevaporated in vacuo to give a solid. Recrystallization from hexane gave1-(2,6-dichloro-4-trifluoromethylphenyl)-4,5-dicyano-3-trifluoromethylpyrazolein the form of white crystals (1.8 g), m.p. 80° C.

By proceeding in a similar manner but replacing the5-carbamoyl-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby5-amino-3-carbamoyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazolethere was prepared:

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazolein the form of a white solid, m.p. 214° C.

REFERENCE EXAMPLE 35

5-Carbamoyl-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleused in the above Example 77, was prepared as follows:

5-Carboxy-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(6.0 g; hereinbefore described in Example 75) was added to thionylchloride (30 ml) and the stirred solution heated to reflux for 4 hours.The solvent was evaporated in vacuo, and re-evaporated after addition ofdry toluene (30 ml). The resultant orange oil was dissolved in dry ether(10 ml) and added dropwise to a stirred solution of ammonia (0.88, 20ml) cooled by an ice bath. After stirring overnight, water (150 ml) wasadded, and the mixture extracted with dichloromethane (3×50 ml). Thecombined extract was washed with water, dried over anhydrous magnesiumsulphate, and evaporated in vacuo to give a white solid (7.0 g).Recrystallization from a mixture of ethyl acetate and petroleum ethergave the title compound (4.3 g), in the form of white crystals, m.p.180°-181° C.

5-Amino-3-carbamoyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazoleused in the above Example 77 was prepared by the same procedure, but byreplacing the5-carboxy-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby5-amino-3-carboxy-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazole.The title compound was obtained in the form of an off-white solid, m.p.223°-224° C.

5-Amino-3-carboxy-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methanesulphonylpyrazoleused above was prepared as follows:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-methanesulphonylpyrazole(8.15 g) was added to stirred 80% sulphuric acid (80 ml), and heated at100° C. for 5 hours. After cooling, the solution was poured onto ice,the solid filtered off and dried over phosphorous pentoxide in a vacuumdesiccator. Recrystallization from a mixture of methanol and petroleumether gave the title compound as a white solid, m.p. 203°-205° C.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-methanesulphonylpyrazole,used above, was prepared by the procedure of Reference Example 23, byreplacing malononitrile by methanesulphonylacetonitrile. The titlecompound was obtained in the form of a white solid, m.p. 255° C., afterrecrystallization from ethanol.

EXAMPLE 78 Compound No. 215

A solution of methylmagnesium iodide (prepared from magnesium (0.26 g)and methyl iodide (1.5 g) in diethyl ether (25 ml)), was treated with asolution of1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano-3-trifluoromethylpyrazole(2 g) in diethyl ether (20 ml), dropwise. The resulting pale yellowsolution was refluxed for 24 hours, cooled, and treated withhydrochloric acid (2N, 10 ml). After stirring for 0.5 hour at roomtemperature, the reaction mixture was diluted with ether (50 ml). Theethereal extract was washed with water (50 ml), dried over anhydrousmagnesium sulphate, and evaporated in vacuo to give a yellow gum. Thiswas purified by chromatography on silica (Merck, 230-400 mesh, 0.7 kgcm⁻²) eluting with a mixture of dichloromethane and petroleum ether(4:1) to give4-acetyl-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleas a white solid, m.p. 134° C.

EXAMPLE 79 Compounds Nos. 216-224

A stirred solution of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthio-3-trifluoromethylpyrazole(1.0 g) in chloroform (40 ml) was treated with m-chloroperbenzoic acid(0.42 g), portionwise at room temperature. After stirring for 6 hours,the solution was diluted with dichloromethane and washed in turn withsodium sulphite solution, sodium hydroxide solution, and water. Thesolution was dried over anhydrous magnesium sulphate, and evaporated invacuo to give a yellow oil. Purification by chromatography on silica(Merck, 230-400 mesh, 0.7 kg cm⁻²) eluting withdichloromethane-ethylacetate (4:1) gave5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylsulphinyl-3-trifluoromethylpyrazolein the form of a white solid, m.p. 142°-145° C. with decomposition.

By proceeding in a similar manner but replacing5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthio-3-trifluoromethylpyrazoleby the appropriate alkylthio phenylpyrazoles there were prepared:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulphinyl-3-trifluoromethylpyrazolein the form of a white solid, m.p. 170° C. from5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthio-3-trifluoromethylpyrazole.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulphinyl-3-methylpyrazolein the form of a buff solid, m.p. 157°-158° C. from5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthio-3-methylpyrazole.

5-Amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylsulphinylphenyl)-3-trifluoromethylpyrazole,in the form of an orange solid, m.p. 76° C., from5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylthiophenyl)-3-trifluoromethylpyrazole.

4-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methylsulphinyl-3-trifluoromethylpyrazole,in the form of white crystals, m.p. 97°-98° C., from4-cyano-1-(2,6-dichlorotrifluoromethylphenyl)-5-methylthio-3-trifluoromethylpyrazole.

By proceeding in a similar manner but replacing5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthio-3-trifluoromethylpyrazoleby the appropriate alkylthiophenylpyrazoles, and employing 2 molarequivalents of m-chloroperbenzoic acid there was prepared:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulphonyl-3-trifluoromethylpyrazole,in the form of white crystals, m.p. 206°-207° C., from5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthio-3-trifluoromethylpyrazole.

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulphonyl-3-methylpyrazole,in the form of a white solid, m.p. 193° C., from5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthio-3-methylpyrazole.

By proceeding in a similar manner but replacing the5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthio-3-trifluoromethylpyrazoleby5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-n-propylthio-3-methylpyrazole,there was obtained5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-propanesulphonylpyrazolein the form of a white solid, m.p. 145.5°-147° C.

By proceeding in a similar manner there was prepared:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trichloromethanesulphonyl-3-methylpyrazolein the form of a pale pink solid, m.p. 183°-184° C., from5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trichloromethylthio-3-methylpyrazole.

EXAMPLE 80 Compounds Nos. 225, 226 and 227

A mixture ofbis[5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazole-4-yl]-disulphide(4.0 g), sodium dithionite (2.02 g) and sodium hydroxide (0.46 g) wasstirred and heated under reflux in a mixture of ethanol and water (60ml, 1:1) for 4 hours. The cooled yellow solution was treated with ethyliodide (2.17 g) and the mixture stirred and heated under reflux for 2hours. After evaporation in vacuo, the yellow gum was dissolved in ether(100 ml), washed with water, dried over anhydrous magnesium sulphate,and re-evaporated in vacuo. The resultant gum was purified bychromatography on silica (Merck, 230-400 mesh, 0.7 kg cm⁻²) eluting withdichloromethane, to furnish5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthio-3-methylpyrazolein the form of a white solid, m.p. 117° C., after recrystallization fromhexane.

By proceeding in a similar manner, but replacing the ethyl iodide bymethyl iodide there was prepared:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-methylthiopyrazole,in the form of a white solid, m.p. 112° C., after recrystallization fromhexane.

By proceeding in a similar manner but replacing the sodium hydroxide bysodium carbonate, and the methyl iodide by n-propyl iodide, there wasobtained5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-n-propylthio-3-methylpyrazolein the form of a white solid, m.p. 100°-102° C.

REFERENCE EXAMPLE 36

Bis[5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazole-4-yl]disulphidewas prepared as follows:

A solution of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-thiocyanatopyrazole(3.0 g; hereinafter described in Example 82) in a mixture of ethanol andwater (1:1, 100 ml) was acidified by the addition of hydrochloric acid(10N, 20 ml). The mixture was heated under reflux for 8 hours,concentrated to half volume in vacuo, cooled in an ice bath, and sodiumhydroxide solution added until the pH reached 9-10. The precipitatedproduct was filtered, washed with water, and dried in vacuo to furnishthe title compound (2.68 g) as an amorphous yellow powder, m.p.211°-213° C.

EXAMPLE 81 Compounds Nos. 228 and 229

A solution of ethyl magnesium bromide, prepared from magnesium (0.57 g)and ethyl bromide (2.6 g) in dry diethyl ether (25 ml), was addeddropwise to a stirred solution of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-thiocyanato-3-trifluoromethylpyrazole(5.0 g) in dry ether (50 ml) at -20° C. After stirring for a further 2hours at room temperature, water (130 ml) was carefully added, andstirring maintained for 0.25 hour. The ether layer was separated, driedover anhydrous magnesium sulphate, and evaporated in vacuo to give ayellow gum. Purification by chromatography on silica (Merck, 230-400mesh, 0.7 kg cm⁻²) eluting with dichloromethane-petroleum ether (1:1)gave a product, which recrystallized from hexane to furnish5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthio-3-trifluoromethylpyrazole,in the form of white needles, m.p. 116°-116.5° C.

By proceeding in a similar manner, but replacing the ethyl magnesiumiodide by methyl magnesium iodide there was obtained:

5-Amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylthio-3-trifluoromethylpyrazole,in the form of a white solid, m.p. 108° C., after recrystallization fromhexane.

EXAMPLE 82 Compounds Nos. 230 and 231

A stirred mixture of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(0.7 g) and potassium thiocyanate (0.55 g) in methanol (15 ml) wastreated with a solution of bromine (0.3 g) in methanol (2 ml) at 0°-5°C. Stirring was maintained at this temperature for 1.5 hours, and themixture was poured onto ice water, and brought to pH 9 by the additionof sodium carbonate. The product was filtered, washed with water anddried. Purification by chromatography on silica (Merck, 230-400 mesh,0.7 kg cm⁻²) eluting with dichloromethane gave5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-thiocyanato-3-trifluoromethylpyrazole,in the form of a white solid, m.p. 49°-50° C.

By proceeding in a similar manner but replacing5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazoleby 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazolethere was obtained5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-thiocyanatopyrazolein the form of a white solid, m.p. 133.5° C., after recrystallizationfrom a mixture of hexane and ethyl acetate.

EXAMPLE 83 Compound No. 232

By proceeding in a similar manner to that hereinbefore described inExample 36, but replacing the2,6-dichloro-4-trifluoromethylphenylhydrazine by2,6-dichloro-4-methanesulphonylphenylhydrazine there was obtained:

5-Amino-4-cyano-1-(2,6-dichloro-4-methanesulphonylphenyl)-3-trifluoromethylpyrazolein the form of white crystals, m.p. 270°-272° C.

REFERENCE EXAMPLE 37

By proceeding in a similar manner to that hereinbefore described inReference Example 19, but replacing the2,6-dichloro-4-trifluoromethylaniline by2,6-dichloro-4-methanesulphonylaniline, there was prepared:

2,6-Dichloro-4-methanesulphonylphenylhydrazine in the form of whitecrystals, m.p. 163°-166° C.

EXAMPLE 84 Compound No. 233

To a stirred ice cold solution of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methylpyrazole (2.0g) in chloroform (40 ml) and pyridine (0.51 g) was added dropwise asolution of trichloromethanesulphenyl chloride (1.2 g) in chloroform (10ml). The resulting brown solution was stirred at 0° C. for 2 hours, thenat room temperature for 2 hours. A further addition oftrichloromethanesulphenyl chloride (0.5 g) was made and the mixturestirred for 2 hours at room temperature. Water (100 ml) anddichloromethane (100 ml) was then added and the organic layer washedwith water (1×100 ml), dried over anhydrous magnesium sulphate andevaporated in vacuo to give a yellow gum (2.9 g). This was purified bychromatography on silica (Merck, 100-230 mesh, 0.7 kg cm⁻²) eluting withdichloromethane petroleum ether (3:2) to give a white solid (0.98 g).Recrystallization from hexane gave5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl-4-trichloromethylthiopyrazolein the form of white crystals, m.p. 156° C.

EXAMPLE 85 Compound No. 234

m-Chloroperbenzoic acid (2.1 g) was added to a solution of5-amino-4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(2.3 g) in dichloromethane (20 ml) cooled to 10° C. After stirringovernight at room temperature, the solution was heated under reflux for4 hours, cooled, and a further addition of m-chloroperbenzoic acid (2.1g) made. The mixture was stirred at room temperature for 4 hours andheated under reflux for 4 hours. The cooled solution was washed withsodium bicarbonate solution (20×20 ml), then with water (2×20 ml), driedover anhydrous magnesium sulphate, filtered, and evaporated in vacuo togive an orange solid. Purification by chromatography on silica (Merck,100-230 mesh, 0.7 kg cm⁻²) eluting with ethyl acetate-petroleum ether(1:9) gave4-cyano-1-(2,6-dichloro-4-trifluoromethanesulphonylphenyl)-5-nitro-3-trifluoromethylpyrazole(0.5 g) in the form of an orange solid, m.p. 168°-169° C.

EXAMPLE 86 Compound No. 235

To a stirred solution of diethylaminosulphur trifluoride (1.5 g) indichloromethane (13 ml) cooled to -70° C., was added dropwise undernitrogen a solution of1-(2,6-dichloro-4-trifluoromethylphenyl)-4-formyl-3-trifluoromethylpyrazole(3.1 g) in dichloromethane (17 ml). After 1 hour at -70° C., the mixturewas allowed to stand at room temperature overnight, then poured ontoexcess iced water. Extraction with dichloromethane gave a solution whichwas washed with water (2×), dried over anhydrous magnesium sulphate andevaporated in vacuo to give a brown oil (3.26 g). Purification bychromatography on silica (Merck, 40-230 mesh, 0.7 kg cm⁻²) eluting withhexane-ethyl acetate (5:1) gave1-(2,6-dichloro-4-trifluoromethylphenyl)-4-difluoromethyl-3-trifluoromethylpyrazole(1.15 g) (from ethyl acetate-hexane) in the form of a pale yellow solid,m.p. 88°-90° C.

REFERENCE EXAMPLE 38

A mixture of4-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(5.0 g; hereinbefore described in Example 53) and formic acid (120 ml)was treated with Raney nickel (5.1 g) and the mixture heated underreflux overnight. After cooling, the mixture was filtered, and thefiltrate diluted with water (900 ml) and extracted with dichloromethane(4×100 ml). The combined extract was washed with sodium bicarbonatesolution (2×), then with water (1×), dried over anhydrous magnesiumsulphate, and evaporated in vacuo to give a brown solid (3.7 g), m.p.80°-82° C. This was1-(2,6-dichloro-4-trifluoromethylphenyl)-4-formyl-3-trifluoromethylpyrazole.

EXAMPLE 87 Compound 236

To a stirred solution of5-amino-4-carboxy-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoromethylpyrazole(15.0 g; hereinbefore described in Reference Example 24) in drytetrahydrofuran (50 ml) was added, under nitrogen, a solution ofboranetetrahydrofuran complex (1 Molar, 27.5 g) during 10 minuteskeeping at -20° C. The solution was allowed to reach room temperatureand stirred overnight. A further addition of the borane was made (10ml), and the solution heated under reflux overnight. After cooling, afurther addition of the borane (20 ml) was made, and the solution againheated under reflux for 4 hours. After cooling, sodium hydroxide (6N)solution was added to pH 11, and the solution extracted withdichloromethane. The organic phase was washed with water, dried overanhydrous magnesium sulphate, and evaporated in vacuo to give a brownoil. Purification by chromatography on silica (Merck, 40-230 mesh, 0.7kg cm⁻²) eluting with hexane-ethyl acetate (2:1) gave5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methyl-3-trifluoromethylpyrazole(2.0 g) from toluene-hexane, m.p. 97°-100° C., in the form of whitecrystals.

LIST OF FORMULAE ##STR3##

In the above formulae it is to be understood that:

A^(a) represents ##STR4##

A^(b) represents ##STR5##

A^(c) represents ##STR6##

We claim:
 1. A compound of the formula:wherein: R^(1') is cyano, nitro, halogen, acetyl, formyl, amino, 1-hydroxyethyl, carboxy, carbamoyl, or straight or branched-chain alkoxycarbonyl or alkoxycarbonylamino of 2 to 7 carbon atoms; R^(2') is R'SO₂, R'SO or R'S in which R' is straight- or branched-chain alkyl, alkenyl or alkynyl of up to 4 carbon atoms which is unsubstituted or substituted by one or more halogen which are the same or different; or R^(2') is hydrogen, thiocyanato, formyl, cyano, carboxy, or straight- or branched-chain alkoxycarbonyl of 2 to 7 carbon atoms; R^(3') is hydrogen or --NR"R"' wherein R" and R"', which are the same or different, each represent hydrogen, straight- or branched-chain alkyl, alkenylalkyl or alkynylalkyl of up to 5 carbon atoms, formyl or straight- or branched-chain alkanoyl of 2 to 5 carbon atoms which is unsubstituted or substituted by one or more halogen atoms, or R" and R"' together with the nitrogen atom to which they are attached form a 5 or 6 membered cyclic imide, or is straight- or branched-chain alkoxycarbonyl of 2 to 5 carbon atoms which is unsubstituted or substituted by one or more halogen, or R^(3') is straight- or branched-chain alkoxymethyleneamino of 2 to 5 carbon atoms which is unsubstituted or substituted on methylene by straight or branched-chain alkyl of 1 to 4 carbon atoms, or R^(3') is halogen or diphenoxycarbonylamino; R⁴ is fluorine, chlorine, bromine or iodine; R⁶ is straight- or branched-chain alkyl or alkoxy of 1 to 4 carbon atoms, which is unsubstituted or substituted by one or more halogen atoms which are the same or different, or chlorine or bromine; R⁵ and R⁷ are hydrogen; and R⁸ is hydrogen, fluorine, chlorine, bromine or iodine; excluding:(1) a compound of the formula: ##STR7## wherein: R¹ is cyano, nitro, halogen, acetyl or formyl; R² is R'SO₂, R'SO or R'S in which R' is straight- or branched-chain alkyl, alkenyl or alkynyl of up to 4 carbon atoms, which is unsubstituted or substituted by one or more halogen which are the same or different; R³ is hydrogen or --NR"R"' wherein R" and R"', which are the same or different, each represent hydrogen, straight- or branched-chain alkyl, alkenylalkyl or alkynylalkyl of up to 5 carbon atoms, formyl or straight- or branched-chain alkanoyl of 2 to 5 carbon atoms which is unsubstituted or substituted by one or more halogen atoms, or R" and R"' together with the nitrogen atom to which they are attached form a 5 or 6 membered cyclic imide, or is straight- or branched-chain alkoxycarbonyl of 2 to 5 carbon atoms which is unsubstituted or substituted by one or more halogen, or R³ is straight- or branched-chain alkoxymethyleneamino of 2 to 5 carbon atoms which is unsubstituted or substituted on methylene by straight- or branched-chain alkyl of 1 to 4 carbon atoms, or R³ is halogen; and R⁴, R⁵, R⁶, R⁷ and R⁸ are as defined above;(2) a compound of formula (XXV) above, wherein the group ##STR8## is 2,6-dichloro-4-trifluoromethylphenyl, R^(2') is cyano, and: (a) R^(1') is cyano and R^(3') is amino, acetamido, dichloroacetamido, t-butylcarbonylamino, propionamido, pentanamido, bis(ethoxycarbonyl)amino, ethoxycarbonylamino, methylamino or ethylamino;(b) R^(1') is chlorine and R^(3') is amino, t-butylcarbonylamino, bis(ethoxycarbonyl)amino or ethoxycarbonylamino; (c) R^(1') is bromine, iodine, amino or ethoxycarbonyl and R^(3') is amino; (d) R^(1') is fluorine and R^(3') is hydrogen or amino; or (e) R^(1') is nitro, amino, t-butoxycarbonylamino or ethoxycarbonyl and R^(3') is hydrogen; (3) a compound of formula (XXV) above, wherein the group ##STR9## is 2,4,6-trichlorophenyl, 2-chloro-4-trifluoromethylphenyl or 2,6-dichloro-4-trifluoromethoxyphenyl, R^(2') is cyano, R^(1') is cyano and R^(3') is amino; (4) a compound of formula (XXV) above, wherein the group ##STR10## is 2,6-dichloro-4-trifluoromethoxyphenyl, R^(2') is cyano, R^(1') is chlorine and R^(3') is amino; (5) a compound of formula (XXV) above, wherein the group ##STR11## is 2,6-dichloro-4-trifluoromethylphenyl, R^(2') is methanesulphonyl, R^(1') is carboxy, carbamoyl or ethoxycarbonyl, and R^(3') is amino.
 2. A compound of the formula: ##STR12## wherein: R¹ is amino, hydroxymethyl, carboxy, carbamoyl or straight- or branched-chain alkoxycarbonyl or alkoxycarbonylamino of 2 to 7 carbon atoms;R² is hydrogen, formyl, carboxy, straight- or branched-chain alkanoyl of 2 to 6 carbon atoms which is substituted by one or more halogen atoms, amino, --SO₂ Cl, or straight- or branched-chain carboxyalkyl of 2 to 6 carbon atoms; R³ is carbamoyl, straight- or branched-chain alkoxycarbonyl of 2 to 7 carbon atoms, or diphenoxycarbonylamino; and R⁴ to R⁸ represent 2,4,6-trichloro, 2,3,5,6-tetrachloro, 2-chloro-4-trifluoromethyl, 2,3,5,6-tetrafluoro-4-trifluoromethyl, 2,6-dichloro-4-trifluoromethylthio, 2-chloro-3,5,6-trifluoro-4-trifluoromethyl, 2,6-dichloro-3,5-difluoro-4-trifluoromethyl, 2,6-dichloro-4-nitro, 2,6-dichloro-4-trifluoromethylsulphinyl, 2,6-dichloro-4-methanesulphonyl or 2,6-dichloro-4-trifluoromethanesulphonyl substitution.
 3. A compound of the formula: ##STR13## wherein: R¹ is amino, hydroxymethyl, carboxy, carbamoyl or straight- or branched-chain alkoxycarbonyl or alkoxycarbonylamino of 2 to 7 carbon atoms;R² is hydrogen, formyl, carboxy, straight- or branched-chain alkanoyl of 2 to 6 carbon atoms which is substituted by one or more halogen atoms, amino, --SO₂ Cl, or straight- or branched-chain carboxyalkyl of 2 to 6 carbon atoms; R³ is carbamoyl, straight- or branched-chain alkoxycarbonyl of 2 to 7 carbon atoms, or diphenoxycarbonylamino; and R⁴ to R⁸ represent 2,6-dichloro-4-trifluoromethyl or 2,6-dichloro-4-trifluoromethoxy substitution. 